WO2025111283A1

WO2025111283A1 - Methods and compositions for the treatment of neurological diseases and disorders

Info

Publication number: WO2025111283A1
Application number: PCT/US2024/056558
Authority: WO
Inventors: Hudson H. Freeze; Bobby G. NG; Matthew Gentry; Juan Pascual; Ramon C. Sun; Craig W. VANDER KOOI
Original assignee: University of Florida; Sanford Burnham Prebys Medical Discovery Institute; University of Texas System; University of Florida Research Foundation Inc; University of Texas at Austin
Current assignee: University of Florida; Sanford Burnham Prebys Medical Discovery Institute; University of Texas System; University of Florida Research Foundation Inc; University of Texas at Austin
Priority date: 2023-11-21
Filing date: 2024-11-19
Publication date: 2025-05-30
Anticipated expiration: 2026-05-21

Abstract

Provided herein are methods and compositions suitable for treating a subject with a neurological or neurodegenerative disease or disorder. In some cases, the treatment comprises administering a therapeutically effective amount of a biologically active sugar to the subject.

Description

METHODS AND COMPOSITIONS FOR THE TREATMENT OF NEUROLOGICAL DISEASES AND DISORDERS

CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of U.S. Provisional Application No. 63/601,670, filed November 21, 2023, which is incorporated herein by reference in its entirety.

STATEMENT AS TO FEDERALLY SPONSORED RESEARCH

[0002] This invention was made with government support under R01 DK099551 awarded by the National Institutes of Health. The government has certain rights in the invention.

BACKGROUND

[0003] Mutations in the glucose transporter 1 (GLUT1) can reduce glucose uptake in the brain by about 50%, resulting in neurological diseases and disorders such as GLUT1 deficiency syndrome. While current treatment includes methods such as ketogenic diets, these methods are not universally effective in all patients. Therefore, there exists a need in the art for new and improved methods and compositions for the treatment of neurological diseases and disorders such as GLUT1 deficiency syndrome.

SUMMARY

[0004] Described herein are methods for treating a subject having a neurological disease or disorder with a therapeutically effective amount of a biologically active sugar.

[0005] In some aspects, described herein is a method of treating a subject with a neurological or neurodegenerative disease or disorder comprising administering a therapeutically effective amount of a biologically active sugar to the subject.

[0006] In some embodiments, the neurological or neurodegenerative disease or disorder comprises a mutation in a gene encoding a solute carrier (SLC) protein . In some cases, the subject is also on a ketogenic diet.

[0007] In some aspects, described herein is a method of treating a subject with a mutation of a gene encoding a family 2 or family 5 solute carrier (SLC) protein, wherein the method comprises administering a therapeutically effective amount of a biologically active sugar to the subject.

[0008] In some cases, the methods described herein comprise restoring the relative abundance of total glycogen and restoring the relative abundance of total glycans in a subject.

[0009] In some aspects, described herein is a method of treating a subject with a mutation of a gene encoding a family 2 or 5 solute carrier (SLC) protein, wherein the method comprises administering a therapeutically effective amount of L-fucose to the subject. [0010] In some aspects, described herein is a method of treating a subject with a mutation of a gene encoding a glucose transporter, wherein the method comprises administering a therapeutically effective amount of a biologically active sugar to the subject. In some cases, the glucose transporter gene encodes a solute carrier (SLC) protein . In some embodiments, the subject is less than 14 years old.

[0011] In some aspects, described herein is a method of treating a subject with GLUT1 deficiency syndrome, wherein the method comprises administering a therapeutically effective amount of a biologically active sugar to the subject at least once a day. In some cases, the biologically active sugar is L-fucose.

[0012] In some cases, a subject of the disclosure is administered a ketogenic diet, wherein the ketogenic diet is a classical ketogenic diet (3 : 1 or 4:1 ratio)), a modified ketogenic diet (2:1 or 1 :1 ratios) or a modified Atkins Diet.

[0013] In some embodiments, a subject is less than 5 years old.

[0014] In some embodiments, the GLUT1 deficiency syndrome comprises a mutation in a gene encoding a solute carrier (SLC) protein.

[0015] In some embodiments, the gene encoding the SLC protein is from family 2 (SLC2) or family 5 (SLC5). In some cases, the gene encoding the SLC protein is SLC2 member Al (SLC2A1).

[0016] In some embodiments, the protein encoded by the SLC2A1 gene is glucose transporter 1 (GLUT 1).

[0017] In some embodiments, a biologically active sugar comprises a monosaccharide, a neutral monosaccharide, a hexose monosaccharide, a deoxyhexose monosaccharide, a 6-deoxyhexose monosaccharide, a 6-deoxyhexose monosaccharide in an L-conformation, L-fucose, and/or any combination thereof. In some embodiments, the biologically active sugar is a monosaccharide. In some embodiments, the monosaccharide is a neutral monosaccharide. In some embodiments, the neutral monosaccharide is a hexose monosaccharide. In some embodiments, the hexose monosaccharide is a deoxyhexose monosaccharide. In some embodiments, the deoxyhexose monosaccharide is a 6-deoxyhexose monosaccharide. In some embodiments, the 6-deoxyhexose monosaccharide is in an L-conformation. In some embodiments, the 6-deoxyhexose monosaccharide is L-fucose

[0018] In some embodiments, a subject as disclosed herein is a subject that is diagnosed as experiencing at least one seizure prior to treatment.

[0019] In some cases, a method as described herein comprises restoring relative abundance of total glycogen in a subject, wherein restoring the relative abundance of total glycogen in the subject comprises increasing an amount of total glycogen in the subject administered a biologically active sugar about 5% to about 100% as compared to a subject that is not administered the biologically active sugar. In some embodiments, restoring the relative abundance of total glycogen in the subject comprises increasing an amount of total glycogen in the subject administered the biologically active sugar 5% to 100% as compared to a subject that is not administered the biologically active sugar. In some cases, restoring the relative abundance of total glycogen in the subject comprises increasing an amount of total glycogen in the subject administered the biologically active sugar at least 10%, at least 20%, at least 30%, at least 40%, or at least 50%, as compared to a subject that is not administered the biologically active sugar. In some cases, restoring the relative abundance of total glycogen in the subject comprises increasing an amount of total glycogen in the subject administered the biologically active sugar greater than 10%, greater than 20%, greater than 30%, greater than 40%, or greater than 50% as compared to a subject that is not administered the biologically active sugar.

[0020] In some aspects, a method as described herein comprises restoring chain length distribution of glycogen and glycans in a subject.

[0021] In some embodiments, a method as described herein comprises restoring relative abundance of total glycans in the subject, and wherein restoring the relative abundance of total glycans in the subject comprises increasing an amount of total glycans in the subject administered the biologically active sugar about 5% to about 100% as compared to a subject that is not administered the biologically active sugar.

[0022] In some cases, restoring the relative abundance of total glycans in the subject comprises increasing an amount of total glycans in the subject administered the biologically active sugar 5% to 100% as compared to a subject that is not administered the biologically active sugar. In some cases, restoring the relative abundance of total glycans in the subject comprises increasing an amount of total glycans in the subject administered the biologically active sugar at least 10%, at least 20%, at least 30%, at least 40%, or at least 50%, as compared to a subject that is not administered the biologically active sugar. In some cases, restoring the relative abundance of total glycans in the subject comprises increasing an amount of total glycans in the subject administered the biologically active sugar greater than 10%, greater than 20%, greater than 30%, greater than 40%, or greater than 50% as compared to a subject that is not administered the biologically active sugar.

[0023] In some cases, a method as described herein comprises restoring gait in a subject.

[0024] In some embodiments, restoring the relative abundance of total glycogen, restoring the chain length distribution of glycogen and glycans, and restoring the relative abundance of total glycans in a subject comprises restoring the relative abundance of total glycogen, restoring the chain length distribution of glycogen and glycans, and restoring the relative abundance of total glycans in the brain of a subject.

[0025] In some aspects, a method as described herein is suitable for a subject wherein the subject has reduced glucose uptake. In some embodiments, the reduced glucose uptake in reduced glucose uptake in the brain of the subject.

[0026] In some embodiments, a neurological or neurodegenerative disease or disorder comprises GLUT1 deficiency syndrome.

[0027] In some embodiments, the administering comprises delivering a biologically active sugar to the subject via oral, subcutaneous, intravenous, or intraperitoneal administration.

[0028] In some cases, a subject as described herein comprises a mammal. In some cases, the subject is a mammal. In some cases, the subject is a human.

[0029] In some aspects, a method of treating a neurological or neurodegenerative disease or disorder as described herein further comprises administering diazoxide to a subject. In some cases, the subject is taking diazoxide to control blood glucose levels within a target level. In some cases, the target level is blood glucoses of 120-180 mg/dL. In some cases, the diazoxide dose is within a range of 5-20 mg/kg/day.

[0030] In some embodiments, a subject as described herein has experienced absence seizures prior to treatment. In some cases, the absence seizures are early-onset absence seizures. In some cases, the subject has epilepsy.

[0031] In some embodiments, the subject is a neonate, infant, child, adolescent, or adult according to American Medical Associations’ age designations. In some embodiments, the subject is a neonate, infant, child, or adolescent according to American Medical Associations’ age designations. In some embodiments, the subject is a neonate, infant, or child according to American Medical Associations’ age designations. In some embodiments, the subject is a neonate or infant according to American Medical Associations’ age designations. In some cases, the subject is male, female or intersex according to American Medical Associations’ definitions. In some cases, the subject is male according to American Medical Associations’ definition . In some cases, the subject is female according to American Medical Associations’ definition. In some cases, the subject is intersex according to American Medical Associations’ definition.

[0032] Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in this art from the following detailed description, wherein only illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.

INCORPORATION BY REFERENCE

[0033] All publications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. For example, Ng B.G., et al. GLUT1 is a highly efficient L-fucose transporter. J. Biol. Chem. (2023) 299(1) 102738. doi: 10.1016/j.jbc.2022.102738. is incorporated by reference in its entirety for all purposes.

BRIEF DESCRIPTION OF THE DRAWINGS

[0034] The novel features of the disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings of which:

[0035] FIG. 1 A depicts a schematic demonstrating the de novo and salvage fucosylation pathways and the siRNA lectin assay workflow.

[0036] FIG. IB shows a graph depicting data demonstrating the saturation of Aleuria aurantia lectin (AAL) staining in increasing concentrations of exogenous L-fucose.

[0037] FIG. 1C shows the top hits identified during the siRNA assay exhibiting decreased AAL binding.

[0038] FIG. 2A shows a graph of L-fucose uptake in the presence ofthe GLUT1 inhibitor BAY- 876 at increasing concentrations.

[0039] FIG. 2B shows a graph of L-fucose uptake in the presence of the GLUT1 inhibitor WZB1 17 at increasing concentrations.

[0040] FIG. 2C shows a graph of L-fucose uptake in the presence of the macropinocytosis inhibitor amiloride at increasing concentrations.

[0041] FIG. 2D shows a graph of L-fucose uptake in the presence ofthe BAY-876 andamiloride at increasing concentrations.

[0042] FIG. 2E shows a graph of L-fucose uptake in the presence of the endocytosis inhibitor Dynasore at increasing concentrations.

[0043] FIG. 2F shows a graph of L-fucose uptake in the presence of the endocytosis inhibitor methyl-P-cyclodextrin at increasing concentrations.

[0044] FIG. 3A shows a graph of ³H-L-fucose uptake using HCT116 (upper) or HepG2 (lower) cells in the presence of clathrin (36 pM Dynasore) and caveolin (4 mM MBCD)-dependent endocytosis inhibitors, GLUT1 inhibitor (100 pM BAY-876) and macropinocytosis inhibitor (500 pM amiloride).

[0045] FIG. 3B shows a graph of ³H-L-fucose uptake using HCT116 (upper) or HepG2 (lower) cells in a presence of increasing concentrations of D-glucose.

[0046] FIG. 3C shows a graph of ³H-L-fucose uptake using HCT116 (upper) or HepG2 (lower) cells in a presence of increasing concentrations of L-glucose.

[0047] FIG. 4A shows a Western blot comparison of GLUT1 expression in DLD-1 WT and GLUT1 KO cells.

[0048] FIG. 4B shows graphs comparing three pM ³H-L-fucose and ¹⁴C-2 -deoxy -D-glucose uptake in DLD-1 WT and GLUT1 KO cells in a presence and absence of GLUT1 (100 pMBAY- 876) and macropinocytosis inhibitor (500 pM amiloride).

[0049] FIG. 4C shows a graph of ³H-L-fucoseand ¹⁴C-2 -deoxy -D-glucose taken up by various cell lines.

[0050] FIG. 4D shows a graph of ¹⁴C-2-deoxy -D-glucose taken up by various cell lines in a presence and absence of 50 pM fucose.

[0051] FIG. 5 shows a graph of GS-MS determination of L-fucose serum concentration of free unbound L-fucose in 23 unrelated human subjects.

[0052] FIG. 6A shows a graph of the relative abundance of total glycogen in WT, GLUT1- deficient, WT fed L-fucose, and GLUT 1 -deficient fed L-Fucose mice.

[0053] FIG. 6B shows a graph of glycogen chain length distribution in WT, GLUT 1 -deficient, WT fed L-fucose, and GLUT 1 -deficient fed L-Fucose mice.

[0054] FIG. 6C shows MALDI imaging of brain tissue atm/z 1337 from WT, GLUT 1 -deficient, WT fed L-fucose, and GLUT 1 -deficient fed L-Fucose mice.

[0055] FIG. 7A shows a graph of the relative abundance of total glycans in WT, GLUT1 - deficient, WT fed L-fucose, and GLUT 1 -deficient fed L-Fucose mice.

[0056] FIG. 7B shows MALDI imaging of brain tissue from WT, GLUT 1 -deficient, WT fed L- fucose, and GLUT 1 -deficient fed L-Fucose mice for different glycans.

[0057] FIG. 8A shows the parameters and locations on a mouse used in analyzing gait by stride angle.

[0058] FIG. 8B show the average right side stride angle of WT and GLUT 1 -deficient mice.

[0059] FIG. 8C show the right side stride angle of WT and GLUT 1 -deficient mice administered L-fucose, measured daily.

DETAILED DESCRIPTION

[0060] Disclosed herein are methods for treating a subject with a neurological or neurodegenerative disease or disorder. The subject may be treated with a biologically active sugar. The subject may be a patient. The administration of the biologically active sugar can restore total glycogen in the brain of the patient as compared to a subject without a neurological or neurodegenerative disease or disorder. The administration of the biologically active sugar can restore total glycans in the brain of the patient as compared to a subject without a neurological or neurodegenerative disease or disorder. The administration of the biologically active sugar can restore the gait of a subject as compared to a subject without a neurological or neurodegenerative disease or disorder. The administration of the biologically active sugar to the patient can reduce the occurrence of seizures.

[0061] The neurological or neurodegenerative disease or disorder may be a congenital disease or disorder. The neurological or neurodegenerative disease or disorder may be a GLUT1 deficiency syndrome. The neurological or neurodegenerative disease or disorder may include Alzheimer’s and/or Parkinson’s diseases. The neurological or neurodegenerative disease or disorder may include a glycosylation disorder. The glycosylation disorder may be a congenital glycosylation disorder.

[0062] Definitions

[0063] The term “salt” refers to acid or base salts of a compound described herein having an acidic or basic moiety. Acid salts can be formed by combining a compound having a basic moiety with an acid. Base salts can be formed by combining a compound having an acidic moiety with a base. The salts may be prepared during the final isolation and purification of the compounds.

[0064] The term “acid” refers to a compound that is an electron pair acceptor in an acid -base reaction. An acid can be an inorganic or organic acid.

[0065] The term “inorganic acid” refers to an acid that does not include a carbon bond . Inorganic acids can be a strong acid or a weak acid. Inorganic acids include, but are not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, sulfamic acid, perchloric acid, boric acid, fluorophosphoric acid, and metaphosphoric acid.

[0066] The term “organic acid” refers to an acid including at least one C-H bond, C-F bond, or C-C bond. Organic acids include, but are not limited to, acetic acid, trifluoroacetic acid, benzoic acid, citric acid, formic acid, fumaric acid, glycolic acid, isobutyric acid, lactic acid (DL), lactic acid (D), lactic acid (L), maleic acid, malonic acid, oxalic acid, propionic acid, salicylic acid, succinic acid, caprylic acid, L-(+)-tartaric acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, and camphor-10- sulfonic acid (+).

[0067] The term “base” refers to a compound that is an electron pair donor in an acid -base reaction. The base can be an inorganic base or an organic base. [0068] The term “inorganic base” refers to a base that does not include at least one C-H bond and includes at least one alkali metal or alkaline earth metal. Examples of an inorganic base include, but are not limited to, sodium hydride, potassium hydride, lithium hydride, calcium hydride, barium carbonate, calcium carbonate, cesium carbonate, lithium carbonate, magnesium carbonate, potassium carbonate, sodium carbonate, cesium hydrogen carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, barium hydroxide, calcium hydroxide, cesium hydroxide, lithium hydroxide, magnesium hydroxide, potassium hydroxide, sodium hydroxide. [0069] The term “organic base” refers to a base including at least one C-H bond (e.g., an amine base). In some embodiments, the amine base can be a primary, secondary, or tertiary amine. In some cases, compounds described herein coordinate with an amine base, such as, but not limited to, DIPEA, TEA, ethanolamine, diethanolamine, triethanolamine, tromethamine, meglumine, N- methylglucamine, dicyclohexylamine, and tris(hydroxymethyl)methylamine.

[0070] The term “pharmaceutically acceptable” it is meant the carrier, diluent or excipient must be compatible with the other ingredients of the formulation.

[0071] The term “pharmaceutically acceptable excipient” and “pharmaceutically acceptable carrier” refer to a substance that aids the administration of an active agent to and absorption by a subject and can be included in the compositions of the present disclosure without causing a significant adverse toxicological effect on the patient.

[0072] The term “treat”, “treating” and “treatment” refer to any indicia of success in the treatment or amelioration of an injury, pathology or condition, including any objective or subjective parameter such as abatement; remission; diminishing of symptoms or making the injury, pathology or condition more tolerable to the patient; slowing in the rate of degeneration or decline; making the final point of degeneration less debilitating; improving a patient’ s physical or mental well-being. The treatment or amelioration of symptoms can be based on objective or subjective parameters.

[0073] The term “treatment” and “treating” and the like can also be used to mean obtaining a desired pharmacological and physiological effect. The effect may be prophylactic in terms of preventing or partially preventing a disease, symptom or condition thereof and/or may be therapeutic in terms of a partial or complete cure of a disease, condition, symptom or adverse effect attributed to the disease. The term “treatment” as used herein covers any treatment of a disease in a mammal, particularly a human, and includes: (a) preventing the disease from occurring in a subject which may be predisposed to the diseasebuthas not yet been diagnosed as having it such as a preventive early asymptomatic intervention; (b) inhibiting the disease, i.e., arrestingits development; or relieving the disease, i.e., causing regression of the disease and/or its symptoms or conditions such as improvement or remediation of damage. [0074] Effective treatment can be indicated by an increase in cognitive performance (e.g., memory, reasoning test), reduction of epileptic seizures, their amplitude or frequency and treatment of motor function and movement disorders.

[0075] The term “patient” or “subject” in need thereof refers to a living organism suffering from or prone to a condition that can be treated by administration of a pharmaceutical composition as provided herein. The term “subject” as used herein refers to mammals. For examples, mammals contemplated by the present disclosure include human, primates, domesticated animals such as cattle, sheep, pigs, horses, laboratory rodents, other pets and the like.

[0076] The term “administering” refers to oral administration, administration as a suppository, topical contact, parenteral, intravenous, intraperitoneal, intramuscular, intralesional, intranasal or subcutaneous administration, intrathecal administration, or the implantation of a slow -release device e.g., a mini-osmotic pump, to the subject.

[0077] The term “therapeutically effective amount or dose” or “therapeutically sufficient amount or dose” or “effective or sufficient amount or dose” refer to a dose that produces therapeutic effects for which it is administered. The exact dose will depend on the purpose of the treatment. [0078] The singular form “a”, “an”, and “the” include plural references unless the context clearly dictates otherwise. For example, the term “a cell” includes one or more cells, including mixtures thereof. “A and/or B” is used herein to include all of the following alternatives: “A”, “B”, “A or B”, and “A and B.”

[0079] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the disclosure. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges, and are also encompassed within the disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure.

[0080] As used herein, the modifier “about” when referring to a number or a numerical range means that the number or numerical range referred to is an approximation, for example, within experimental variability and/or statistical experimental error, and thus the number or numerical range may vary up to ±10% of the stated number or numerical range.

[0081] All ranges disclosed herein also encompass any and all possible sub -ranges and combinations of sub -ranges thereof. Any listed range can be recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, and so forth. As a non -limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, and the like. As will also be understood by one skilled in the art all language such as “up to,” “at least,” “greater than,” “less than,” and the like include the number recited and refer to ranges which can be subsequently broken down into sub-ranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member. Thus, for example, a group having 1-3 articles refers to groups having 1, 2, or 3 articles. Similarly, a group having 1 -5 articles refers to groups having 1, 2, 3, 4, or 5 articles, and so forth.

Biologically Active Sugar

[0082] Aspects disclosed herein comprise a biologically active sugar. The biologically active sugar can be a monosaccharide. Non-limiting examples of monosaccharides include erythrose, threose, erythrulose, arabinose, lyxose, ribose, xylose, ribulose, xylulose, glucose, mannose, galactose, allose, altrose, gulose, idose, talose, psicose, fructose, sorbose, tagatose, fucose, and rhamnose. The biologically active sugar can be a disaccharide. Non-limiting examples of disaccharides include cellobiose, gentiobiose, isomaltose, lactose, lactulose, laminaribiose, maltose, mannobiose, melibiose, nigerose, rutinose, sucrose, trehalose, and xylobiose . The biologically active sugar can be an oligosaccharide. The oligosaccharide can have 3, 4, 5, 6, 7, 8, 9, or 10 sugar units. The biologically active sugar can be an L-enantiomer or a D-enantiomer. The biologically active sugar can be in alpha or beta form. The biologically active sugar can be a triose, tetrose, pentose, hexose, or heptose sugar. The biologically active sugar can comprise an aldehyde group. The biologically active sugar can comprise a ketone group. The biologically active sugar can be neutral. The biologically active sugar can be deoxy sugar. The biologically active sugar can be a hexose sugar. The biologically active sugar can be a deoxyhexose sugar. The biologically active sugar can be a 6-deoxyhexose sugar. The biologically active sugar can be fucose. In some embodiments, the biologically active sugar is L-fucose.

Pharmaceutical Compositions

[0083] Aspects disclosed herein comprise pharmaceutical compositions. The pharmaceutical compositions can comprise a biologically active sugar and a pharmaceutically acceptable excipient and/or additive. The pharmaceutical composition can comprise two biologically active sugars. The pharmaceutical composition can comprise a biologically active sugar and another biologically active compound. The composition can also contain other compatible therapeutic agents. In some embodiments, co-administration can be accomplished by co -formulation, e.g., preparing a single pharmaceutical composition including multiple compounds, e.g., the biologically active sugar and another biologically active compound.

[0084] A pharmaceutical composition can comprise a biologically active sugar. A biologically active sugar can comprise a monosaccharide. The monosaccharide can be a neutral monosaccharide. The monosaccharide can be a hexose monosaccharide. Non-limiting examples of hexose monosaccharides include but are not limited to glucose, mannose, galactose, talose, fucose, rhamnose, sorbose, and fructose. The hexose monosaccharide can be a deoxyhexose monosaccharide. Non-limiting examples of deoxyhexose monosaccharides include but are not limited to rhamnose and fucose. The monosaccharide can be a 6-deoxyhexose monosaccharide. In some embodiments, the monosaccharide comprises fucose. The monosaccharide can be in a D-configuration or conformation. The monosaccharide can be in a L-configuration or conformation. In some embodiments, the monosaccharide comprises L-fucose.

[0085] A pharmaceutical composition can comprise L-fucose. In some embodiments, a pharmaceutical composition comprising L-fucose comprises a therapeutically effective amount of L-fucose. A pharmaceutical composition may comprise L-fucose and a pharmaceutical excipient, e.g., a pharmaceutically acceptable excipient. A pharmaceutical composition may comprise L-fucose and a pharmaceutical additive, e.g., a pharmaceutically acceptable additive. A pharmaceutical composition may comprise L-fucose and a salt, e.g., a pharmaceutically acceptable salt. In some embodiments, a pharmaceutical composition may comprise L-fucose and a pharmaceutical excipient, a pharmaceutical additive, a salt, or any combination thereof. Nonlimiting details, descriptions, and properties of pharmaceutically acceptable excipients, additives, and salts are disclosed herein. Non-limiting examples of pharmaceutically acceptable excipients, additives, and salts are disclosed herein.

[0086] A pharmaceutical composition can comprise L-fucose and another biologically active compound. In some embodiments, a pharmaceutical composition comprising L-fucose may comprise a therapeutically effective amount of L-fucose. In some embodiments, a pharmaceutical composition comprising L-fucose and another biologically active compound comprises a therapeutically effective amount of L-fucose. In some embodiments, a pharmaceutical composition comprising L-fucose and another biologically active compound comprises a therapeutically effective amount of the another biologically active compound. In some embodiments, a pharmaceutical composition comprising L-fucose and the another biologically active compound comprises a therapeutically effective amount of L-fucose and a therapeutically effective amount the another biologically active compound. A pharmaceutical composition may comprise L-fucose, another biologically active compound, and a pharmaceutical excipient, e.g., a pharmaceutically acceptable excipient. A pharmaceutical composition may comprise L-fucose, another biologically active compound, and a pharmaceutical additive, e.g., a pharmaceutically acceptable additive. A pharmaceutical composition may comprise L-fucose, another biologically active compound, and a salt, e.g., a pharmaceutically acceptable salt. In some embodiments, a pharmaceutical composition may comprise L-fucose, another biologically active compound, and one or more of a pharmaceutical excipient, a pharmaceutical additive, or a salt. Non-limiting details, descriptions, and properties of pharmaceutically acceptable excipients, additives, and salts are disclosed herein. Non -limiting examples of pharmaceutically acceptable excipients, additives, and salts are disclosed herein.

[0087] The another biologically active compound can comprise a disaccharide. The disaccharide can comprise a homodisaccharide. The disaccharide can comprise glucose. The disaccharide can comprise two units of glucose. The disaccharide can comprise a 1,4-glycosidic linkage. The disaccharide can comprise a 1,1 -glycosidic linkage. The disaccharide can comprise a 1,1 - glycosidic linkage. The disaccharide linkage can comprise an alpha glycosidic linkage, e.g., an alpha- 1,4-glycosidic linkage or an alpha-1,1 -glycosidic linkage. The disaccharide linkage can comprise a beta glycosidic linkage, e.g., a beta-1, 4-glycosidic linkage. Non-limiting examples of homodisaccharides with two units of glucose include but are not limited to maltose, trehalose, and cellobiose. In some embodiments, the another biologically active compound comprises trehalose.

[0088] The another biologically active compound can comprise a bicyclic heterocyclic benzene derivative. The another biologically active compound can comprise a thiazide derivative. The another biologically active compound can comprise a benzothiadiazine. Non-limiting examples of benzothiadiazine can include but are not limited to bemetizide, bentazone, benzthiazide, butizide, diazoxide, epitizide, mebutizide, and teclothiazide. In some embodiments, the another biologically active compound comprises diazoxide.

[0089] The pharmaceutical composition can comprise a salt. In some embodiments, the compounds of the present disclosure include the salt forms thereof. The pharmaceutical composition can comprise a pharmaceutically acceptable excipient. Non-limiting examples of pharmaceutically acceptable excipients include water, NaCl, normal saline solutions, lactated Ringer’s, normal sucrose, normal glucose, binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavors and colors, and the like.

[0090] Suitable solid excipients include, but are not limited to, magnesium carbonate; magnesium stearate; talc; pectin; dextrin; starch; tragacanth; a low melting wax; cocoa butter; carbohydrates; sugars including, but not limited to, lactose, sucrose, mannitol, or sorbitol, starch from corn, wheat, rice, potato, or other plants; cellulose such as methyl cellulose, hydroxypropylmethyl-cellulose, or sodium carboxymethylcellulose; and gums including tragacanth; as well as proteins including, but not limited to, gelatin and collagen. If desired, disintegrating or solubilizing agents may be added, such as the cross-linked polyvinyl pyrrolidone, agar, alginic acid, or a salt thereof, such as sodium alginate. The pharmaceutical compositions disclosed herein can be prepared in a wide variety of oral, parenteral and topical dosage forms.

[0091] The pharmaceutical compositions can comprise a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers can be solid or liquid. Solid form preparations include powders, tablets, capsules, cachets, suppositories, and dispersible granules. A solid carrier can be one or more substances, which may also act as diluents, flavoring agents, binders, preservatives, tablet disintegrating agents, or an encapsulating material.

[0092] In powders, the carrier can be a finely divided solid, which is in a mixture with the finely divided active component. In tablets, the active component can be mixed with the carrier having the necessary binding properties in suitable proportions and compacted in the shape and size desired. The powders and tablets can contain from about 5% or about 10% to about 70% or about 80% of the compound or compounds of the present disclosure. The powders and tablets can contain from about 5% to about 90% of the compound or compounds of the present disclosure. [0093] Oral preparations can include tablets, powder, dragees, capsules, liquids, lozenges, cachets, gels, syrups, slurries, and suspensions. Pharmaceutical preparations of the disclosure can also be used orally using, for example, push -fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a coating such as glycerol or sorbitol. Push-fit capsules can contain the compounds of the present disclosure mixed with a filler or binders such as lactose or starches, lubricants such as talc or magnesium stearate, and, optionally, stabilizers. In soft capsules, the compounds of the present disclosure may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycol with or without stabilizers.

[0094] Liquid form preparations can include solutions, suspensions, and emulsions, for example, water or water/propylene glycol solutions. For parenteral injection, liquid preparations can be formulated in solution in aqueous polyethylene glycol solution. Aqueous solutions suitable for oral use can be prepared by dissolving the compounds of the present disclosure in water and adding suitable colorants, flavors, stabilizers, and thickening agents as desired. Aqueous suspensions suitable for oral use can be made by dispersing the finely divided active component in water with viscous material, such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia, and dispersing or wetting agents such as a naturally occurring phosphatide (e.g., lecithin), a condensation product of an alkylene oxide with a fatty acid (e.g., polyoxyethylene stearate), a condensation product of ethylene oxide with a long chain aliphatic alcohol (e.g., heptadecaethylene oxycetanol), a condensation product of ethylene oxide with a partial ester derived from a fatty acid and a hexitol (e.g., polyoxyethylene sorbitol mono -oleate), or a condensation product of ethylene oxide with a partial ester derived from fatty acid and a hexitol anhydride (e.g., polyoxyethylene sorbitan mono-oleate). The aqueous suspension can also contain one or more preservatives such as ethyl or n-propyl p -hydroxy benzoate, one or more coloring agents, one or more flavoring agents and one or more sweetening agents, such as sucrose, aspartame or saccharin. Formulations can be adjusted for osmolarity.

[0095] Also included are solid form preparations, which are intended to be converted, shortly before use, to liquid form preparations for oral administration. Such liquid forms can include solutions, suspensions, and emulsions. These preparations may contain, in addition to the active component, colorants, flavors, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like.

[0096] In another embodiment, the compositions of the present disclosure can be formulated for parenteral administration, such as intravenous (IV) administration or administration into a body cavity or lumen of an organ. The formulations for administration will commonly comprise a solution of the compositions of the present disclosure dissolved in a pharmaceutically acceptable carrier. Amongthe acceptable vehicles and solvents that can be employed are water and Ringer’s solution, an isotonic sodium chloride. In addition, sterile fixed oils can conventionally be employed as a solvent or suspending medium. For this purpose, any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid can likewise be used in the preparation of injectables. These solutions canbe sterile and generally free of undesirable matter. These formulations may be sterilized by conventional sterilization techniques. The formulations may contain pharmaceutically acceptable auxiliary substances as required to approximate physiological conditions such as pH adjusting and buffering agents, toxicity adjusting agents, e.g., sodium acetate, sodium chloride, potassium chloride, calcium chloride, and sodium lactate. The concentration of the compositions of the present disclosure in these formulations can vary widely, and may be selected primarily based on fluid volumes, viscosities, and body weight, in accordance with the particular mode of administration selected and the patient’s needs. For IV administration, the formulation can be a sterile injectable preparation, such as a sterile injectable aqueous or oleaginous suspension. This suspension canbe formulated using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation can also be a sterile injectable solution or suspension in a nontoxic parenterally acceptable diluent or solvent, such as a solution of 1,3 -butanediol.

Methods Of Treatment

[0097] In one aspect, provided herein is a method of treating a neurological or neurodegenerative disease or disorder. In some embodiments, the method includes administering to a subject in need thereof a therapeutically effective amount of a biologically active sugar as disclosed herein. The method can include administering to a subject in need thereof a therapeutically effective amount of L-fucose as disclosed herein. In some embodiments, the biologically active sugar is administered with another biologically active compound. The another biologically active compound can be formulated with the biologically active sugar. The another biologically active compound can be administered with the biologically active sugar. In some embodiments, L- fucose is administered with an additional biologically active compound. The additional biologically active compound can be formulated with L-fucose. The another biologically active compound can be administered with L-fucose. The additional biologically active compound can be a biologically active sugar. The additional biologically active compound can be a disaccharide. In some embodiments, the additional biologically active compound comprises trehalose. The another biologically active compound can be a benzothiadiazine. In some embodiments, the additional biologically active compound comprises diazoxide.

[0098] The compounds and compositions of the present disclosure, and any other compounds, can be present in any suitable amount, and can depend on various factors including, but not limited to, weight and age of the subject, state of the disease, etc.

[0099] The method of treatment can comprise administering about 20 milligram (mg) per kilogram (kg) body weight per day (mg/kg/day) to about 2000 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 20 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 25 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 30 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 35 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 40 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 45 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 50 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 55 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 60 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 65 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 70 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 75 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 80 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 85 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 90 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 95 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 100 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 125 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 150 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 175 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 200 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 225 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 250 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 275 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 300 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 325 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 350 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 375 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 400 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 425 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 450 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 475 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 500 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 525 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 550 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 575 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 600 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 625 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 650 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 675 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 700 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 725 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 750 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 775 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 800 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 825 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 850 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 875 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 900 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 925 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 950 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 975 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1000 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1025 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1050 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1075 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1100 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1125 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1150 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1175 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1200 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1225 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1250 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1275 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1300 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1325 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1350 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1375 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1400 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1425 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1450 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1475 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1500 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1525 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1550 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1575 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1600 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1625 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1650 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1675 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1700 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1725 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1750 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1775 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1800 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1825 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1850 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1875 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1900 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1925 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1950 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 1975 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 2000 mg/kg/day of a biologically active sugar.

[0100] The method of treatment can comprise administering about 20 mg/kg/day to about 2000 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 25 mg/kg/day to about 1975 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 30 mg/kg/day to about 1950 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 35 mg/kg/day to about 1925 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 40 mg/kg/day to about 1900 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 45 mg/kg/day to about 1875 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 50 mg/kg/day to about 1850 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 55 mg/kg/day to about 1825 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 60 mg/kg/day to about 1800 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 65 mg/kg/day to about 1775 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 70 mg/kg/day to about 1750 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 75 mg/kg/day to about 1725 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 80 mg/kg/day to about 1700 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 85 mg/kg/day to about 1675 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 90 mg/kg/day to about 1650 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 95 mg/kg/day to about 1625 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 100 mg/kg/day to about 1600 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 125 mg/kg/day to about 1575 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 150 mg/kg/day to about 1550 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 175 mg/kg/day to about 1525 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 200 mg/kg/day to about 1500 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 225 mg/kg/day to about 1475 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 250 mg/kg/day to about 1450 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 275 mg/kg/day to about 1425 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 300 mg/kg/day to about 1400 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 325 mg/kg/day to about 1375 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 350 mg/kg/day to about 1350 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 375 mg/kg/day to about 1325 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 400 mg/kg/day to about 1300 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 425 mg/kg/day to about 1275 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 450 mg/kg/day to about 1250 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 475 mg/kg/day to about 1225 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 500 mg/kg/day to about 1200 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 525 mg/kg/day to about 1175 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 550 mg/kg/day to about 1150 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 575 mg/kg/day to about 1125 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 600 mg/kg/day to about 1100 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 625 mg/kg/day to about 1075 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 650 mg/kg/day to about 1050 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 675 mg/kg/day to about 1025 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 700 mg/kg/day to about 1000 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 725 mg/kg/day to about 975 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 750 mg/kg/day to about 950 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 775 mg/kg/day to about 925 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 800 mg/kg/day to about 900 mg/kg/day of a biologically active sugar. The method of treatment can comprise administering about 825 mg/kg/day to about 875 mg/kg/day of a biologically active sugar.

[0101] The method of treatment can comprise administering about 20 mg/kg/day of L-fucose. The method of treatment can comprise administering about 25 mg/kg/day of L-fucose. The method of treatment can comprise administering about 30 mg/kg/day of L-fucose. The method of treatment can comprise administering about 35 mg/kg/day of L-fucose. The method of treatment can comprise administering about 40 mg/kg/day of L-fucose. The method of treatment can comprise administering about 45 mg/kg/day of L-fucose. The method of treatment can comprise administering about 50 mg/kg/day of L-fucose. The method of treatment can comprise administering about 55 mg/kg/day of a L-fucose. The method of treatment can comprise administering about 60 mg/kg/day of L-fucose. The method of treatment can comprise administering about 65 mg/kg/day of L-fucose. The method of treatment can comprise administering about 70 mg/kg/day of L-fucose. The method of treatment can comprise administering about 75 mg/kg/day of L-fucose. The method of treatment can comprise administering about 80 mg/kg/day of L-fucose. The method of treatment can comprise administering about 85 mg/kg/day of L-fucose. The method of treatment can comprise administering about 90 mg/kg/day of L-fucose. The method of treatment can comprise administering about 95 mg/kg/day of L-fucose. The method of treatment can comprise administering about 100 mg/kg/day of L-fucose. The method of treatment can comprise administering about 125 mg/kg/day of L-fucose. The method of treatment can comprise administering about 150 mg/kg/day of L-fucose. The method of treatment can comprise administering about 175 mg/kg/day of L-fucose. The method of treatment can comprise administering about 200 mg/kg/day of L-fucose. The method of treatment can comprise administering about 225 mg/kg/day of L-fucose. The method of treatment can comprise administering about 250 mg/kg/day of L-fucose. The method of treatment can comprise administering about 275 mg/kg/day of L-fucose. The method of treatment can comprise administering about 300 mg/kg/day of L-fucose. The method of treatment can comprise administering about 325 mg/kg/day of L-fucose. The method of treatment can comprise administering about 350 mg/kg/day of L-fucose. The method of treatment can comprise administering about 375 mg/kg/day of L-fucose. The method of treatment can comprise administering about 400 mg/kg/day of L-fucose. The method of treatment can comprise administering about 425 mg/kg/day of L-fucose. The method of treatment can comprise administering about 450 mg/kg/day of L-fucose. The method of treatment can comprise administering about 475 mg/kg/day of L-fucose. The method of treatment can comprise administering about 500 mg/kg/day of L-fucose. The method of treatment can comprise administering about 525 mg/kg/day of L-fucose. The method of treatment can comprise administering about 550 mg/kg/day of L-fucose. The method of treatment can comprise administering about 575 mg/kg/day of L-fucose. The method of treatment can comprise administering about 600 mg/kg/day of L-fucose. The method of treatment can comprise administering about 625 mg/kg/day of L-fucose. The method of treatment can comprise administering about 650 mg/kg/day of L-fucose. The method of treatment can comprise administering about 675 mg/kg/day of L-fucose. The method of treatment can comprise administering about 700 mg/kg/day of L-fucose. The method of treatment can comprise administering about 725 mg/kg/day of L-fucose. The method of treatment can comprise administering about 750 mg/kg/day of L-fucose. The method of treatment can comprise administering about 775 mg/kg/day of L-fucose. The method of treatment can comprise administering about 800 mg/kg/day of L-fucose. The method of treatment can comprise administering about 825 mg/kg/day of L-fucose. The method of treatment can comprise administering about 850 mg/kg/day of L-fucose. The method of treatment can comprise administering about 875 mg/kg/day of L-fucose. The method of treatment can comprise administering about 900 mg/kg/day of L-fucose. The method of treatment can comprise administering about 925 mg/kg/day of L-fucose. The method of treatment can comprise administering about 950 mg/kg/day of L-fucose. The method of treatment can comprise administering about 975 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1000 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1025 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1050 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1075 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1100 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1125 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1150 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1175 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1200 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1225 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1250 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1275 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1300 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1325 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1350 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1375 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1400 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1425 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1450 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1475 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1500 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1525 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1550 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1575 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1600 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1625 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1650 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1675 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1700 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1725 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1750 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1775 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1800 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1825 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1850 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1875 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1900 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1925 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1950 mg/kg/day of L-fucose. The method of treatment can comprise administering about 1975 mg/kg/day of L-fucose. The method of treatment can comprise administering about 2000 mg/kg/day of L-fucose.

[0102] The method of treatment can comprise administering about 20 mg/kg/day to about 2000 mg/kg/day of L-fucose. The method of treatment can comprise administering about 25 mg/kg/day to about 1975 mg/kg/day of L-fucose. The method of treatment can comprise administering about 30 mg/kg/day to about 1950 mg/kg/day of L-fucose. The method of treatment can comprise administering about 35 mg/kg/day to about 1925 mg/kg/day of L-fucose. The method of treatment can comprise administering about 40 mg/kg/day to about 1900 mg/kg/day of L-fucose. The method of treatment can comprise administering about 45 mg/kg/day to about 1875 mg/kg/day of L-fucose. The method of treatment can comprise administering about 50 mg/kg/day to about 1850 mg/kg/day of L-fucose. The method of treatment can comprise administering about 55 mg/kg/day to about 1825 mg/kg/day of L-fucose. The method of treatment can comprise administering about 60 mg/kg/day to about 1800 mg/kg/day of L-fucose. The method of treatment can comprise administering about 65 mg/kg/day to about 1775 mg/kg/day of L-fucose. The method of treatment can comprise administering about 70 mg/kg/day to about 1750 mg/kg/day of L-fucose. The method of treatment can comprise administering about 75 mg/kg/day to about 1725 mg/kg/day of L-fucose. The method of treatment can comprise administering about 80 mg/kg/day to about 1700 mg/kg/day of L-fucose. The method of treatment can comprise administering about 85 mg/kg/day to about 1675 mg/kg/day of L-fucose. The method of treatment can comprise administering about 90 mg/kg/day to about 1650 mg/kg/day of L-fucose. The method of treatment can comprise administering about 95 mg/kg/day to about 1625 mg/kg/day of L-fucose. The method of treatment can comprise administering about 100 mg/kg/day to about 1600 mg/kg/day of L-fucose. The method of treatment can comprise administering about 125 mg/kg/day to about 1575 mg/kg/day of L-fucose. The method of treatment can comprise administering about 150 mg/kg/day to about 1550 mg/kg/day of L-fucose. The method of treatment can comprise administering about 175 mg/kg/day to about 1525 mg/kg/day of L- fucose. The method of treatment can comprise administering about 200 mg/kg/day to about 1500 mg/kg/day of L-fucose. The method of treatment can comprise administering about 225 mg/kg/day to about 1475 mg/kg/day of L-fucose. The method of treatment can comprise administering about 250 mg/kg/day to about 1450 mg/kg/day of L-fucose. The method of treatment can comprise administering about 275 mg/kg/day to about 1425 mg/kg/day of L- fucose. The method of treatment can comprise administering about 300 mg/kg/day to about 1400 mg/kg/day of L-fucose. The method of treatment can comprise administering about 325 mg/kg/day to about 1375 mg/kg/day of L-fucose. The method of treatment can comprise administering about 350 mg/kg/day to about 1350 mg/kg/day of L-fucose. The method of treatment can comprise administering about 375 mg/kg/day to about 1325 mg/kg/day of L- fucose. The method of treatment can comprise administering about 400 mg/kg/day to about 1300 mg/kg/day of L-fucose. The method of treatment can comprise administering about 425 mg/kg/day to about 1275 mg/kg/day of L-fucose. The method of treatment can comprise administering about 450 mg/kg/day to about 1250 mg/kg/day of L-fucose. The method of treatment can comprise administering about 475 mg/kg/day to about 1225 mg/kg/day of L- fucose. The method of treatment can comprise administering about 500 mg/kg/day to about 1200 mg/kg/day of L-fucose. The method of treatment can comprise administering about 525 mg/kg/day to about 1175 mg/kg/day of L-fucose. The method of treatment can comprise administering about 550 mg/kg/day to about 1150 mg/kg/day of L-fucose. The method of treatment can comprise administering about 575 mg/kg/day to about 1125 mg/kg/day of L- fucose. The method of treatment can comprise administering about 600 mg/kg/day to about 1100 mg/kg/day of L-fucose. The method of treatment can comprise administering about 625 mg/kg/day to about 1075 mg/kg/day of L-fucose. The method of treatment can comprise administering about 650 mg/kg/day to about 1050 mg/kg/day of L-fucose. The method of treatment can comprise administering about 675 mg/kg/day to about 1025 mg/kg/day of L- fucose. The method of treatment can comprise administering about 700 mg/kg/day to about 1000 mg/kg/day of L-fucose. The method of treatment can comprise administering about 725 mg/kg/day to about 975 mg/kg/day of L-fucose. The method of treatment can comprise administering about 750 mg/kg/day to about 950 mg/kg/day of L-fucose. The method of treatment can comprise administering about 775 mg/kg/day to about 925 mg/kg/day of L-fucose. The method of treatment can comprise administering about 800 mg/kg/day to about 900 mg/kg/day of L-fucose. The method of treatment can comprise administering about 825 mg/kg/day to about 875 mg/kg/day of L-fucose.

[0103] In some embodiments, the method includes administering another compound (e.g., therapeutic compound). In some embodiments, the method includes administering another compound (e.g., therapeutic compound) in a therapeutically effective amount. In some embodiments, the another compound is an compound for treating a neurological or neurodegenerative disease or disorder. In some embodiments, the another compound is a compound for treating a blood sugar. In some embodiments, the another compound is a compound for treating a low blood sugar. In other embodiments, the another compound is an anti-neurodegenerative compound. In other embodiments, the another compound is an antiseizure compound. [0104] In some embodiments, the method of treatment can comprise administering another compound with L-fucose. In some embodiments, the method of treatment can comprise administering benzothiadiazine with L-fucose. The method of treatment can comprise administering about 1 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 2 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 3 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 4 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 5 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 6 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 7 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 8 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 9 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 10 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 11 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 12 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 13 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 14 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 15 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 16 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 17 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 18 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 19 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 20 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 21 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 22 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 23 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 24 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 25 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 26 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 27 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 28 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 29 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 30 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 31 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 32 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 33 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 34 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 35 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 36 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 37 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 38 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 39 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 40 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 41 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 42 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 43 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 44 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 45 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 46 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 47 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 48 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 49 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 50 mg/kg/day of benzothiadiazine with a therapeutically effective amount of L-fucose.

[0105] In some embodiments, the method of treatment can comprise administering another compound with L-fucose. In some embodiments, the method of treatment can comprise administering diazoxide with L-fucose. The method of treatment can comprise administering about 1 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 2 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 3 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 4 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 5 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 6 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 7 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 8 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 9 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 10 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 11 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 12 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 13 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 14 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 15 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 16 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 17 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 18 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 19 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 20 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 21 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 22 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 23 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 24 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 25 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 26 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 27 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 28 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 29 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 30 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 31 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 32 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 33 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 34 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 35 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 36 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 37 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 38 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 39 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 40 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 41 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 42 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 43 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 44 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 45 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 46 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 47 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 48 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 49 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 50 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose.

[0106] The method of treatment can comprise administering about 1 mg/kg/day to about 50 mg/kg/day of diazoxide. The method of treatment can comprise administering about 2 mg/kg/day to about 45 mg/kg/day of diazoxide. The method of treatment can comprise administering about 3 mg/kg/day to about 40 mg/kg/day of diazoxide. The method of treatment can comprise administering about 4 mg/kg/day to about 35 mg/kg/day of diazoxide. The method of treatment can comprise administering about 5 mg/kg/day to about 30 mg/kg/day of diazoxide. The method of treatment can comprise administering about 6 mg/kg/day to about 25 mg/kg/day of diazoxide. The method of treatment can comprise administering about 7 mg/kg/day to about 20 mg/kg/day of diazoxide. The method of treatment can comprise administering about 8 mg/kg/day to about 15 mg/kg/day of diazoxide. The method of treatment can comprise administering about 9 mg/kg/day to about 10 mg/kg/day of diazoxide. The method of treatment can comprise administering about 5 mg/kg/day to about 20 mg/kg/day of diazoxide.

[0107] The method of treatment can comprise administering about 1 mg/kg/day to about 50 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 2 mg/kg/day to about 45 mg/kg/day of diazoxide. The method of treatment can comprise administering about 3 mg/kg/day to about 40 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 4 mg/kg/day to about 35 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 5 mg/kg/day to about 30 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 6 mg/kg/day to about 25 mg/kg/day of diazoxide with a therapeutically effective amount of L- fucose. The method of treatment can comprise administering about 7 mg/kg/day to about 20 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 8 mg/kg/day to about 15 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 9 mg/kg/day to about 10 mg/kg/day of diazoxide with a therapeutically effective amount of L-fucose. The method of treatment can comprise administering about 5 mg/kg/day to about 20 mg/kg/day of diazoxide with a therapeutically effective amount of L- fucose.

[0108] In some embodiments, the method of treatment can comprise administering another compound with L-fucose. In some embodiments, the method of treatment can comprise administering trehalose with L-fucose. The method of treatment can comprise administering about 100 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 200 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 300 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 400 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 500 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 600 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 700 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 800 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 900 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1000 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1100 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1200 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1300 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1400 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1500 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1600 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1700 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1800 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1900 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2000 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2100 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2200 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2300 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2400 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2500 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2600 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2700 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2800 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2900 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3000 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3100 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3200 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3300 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3400 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3500 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3600 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3700 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3800 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3900 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4000 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4100 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4200 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4300 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4400 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4500 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4600 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4700 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4800 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4900 mg/kg/day of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 5000 mg/kg/day of trehalose with a therapeutically effective amount L-fucose.

[0109] In some embodiments, the method of treatment can comprise administering another compound with L-fucose. In some embodiments, the method of treatment can comprise administering trehalose with L-fucose. The method of treatment can comprise administering about 100 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 200 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 300 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 400 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 500 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 600 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 700 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 800 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 900 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1000 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1100 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1200 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1300 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1400 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1500 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1600 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1700 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1800 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 1900 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2000 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2100 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2200 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2300 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2400 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2500 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2600 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2700 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2800 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 2900 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3000 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3100 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3200 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3300 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3400 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3500 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3600 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3700 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3800 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 3900 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4000 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4100 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4200 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4300 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4400 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4500 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4600 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4700 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4800 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 4900 mg/kg/week of trehalose with a therapeutically effective amount L-fucose. The method of treatment can comprise administering about 5000 mg/kg/week of trehalose with a therapeutically effective amount L-fucose.

[0110] In some embodiments, the method of treatment can comprise administering L-fucose, diazoxide, and trehalose. In some embodiments, the method of treatment can comprise administering therapeutically effective amounts of each of L-fucose, diazoxide, and trehalose. In some embodiments, the method of treatment can comprise administering therapeutically effective amounts of each of L-fucose and diazoxide. In some embodiments, the method of treatment can comprise administering therapeutically effective amounts of each of L-fucose and trehalose. In some embodiments, the method of treatment can comprise administering therapeutically effective amounts of each of L-fucose, diazoxide, and trehalose as disclosed herein. In some embodiments, the method of treatment can comprise administering therapeutically effective amounts of each of L-fucose and diazoxide as disclosed herein. In some embodiments, the method of treatment can comprise administering therapeutically effective amounts of each of L-fucose and trehalose as disclosed herein. The compounds and compositions of the present disclosure, and any other compounds, can be present in any suitable amount, and can depend on various factors including, but not limited to, weight of the subject, age of the subject, and state of disease.

[0111] In some embodiments, the method of treating a subject includes treating a subject who is on a ketogenic diet. In some embodiments, the method of treating a subject includes treating a subject who has had at least one seizure. In some embodiments, the method of treating a subject includes treating a subject who has reduced glucose uptake. In some embodiments, the method of treating a subject includes treating a subject who has epilepsy. In some embodiments, the method of treating a subject includes treating a subject who has reduced total glycogen. In some embodiments, the method of treating a subject includes treating a subject who has reduced total glycogen in the brain. In some embodiments, the method of treating a subject includes treating a subject who has reduced total glycan. In some embodiments, the method of treating a subject includes treating a subject who has reduced total glycan in the brain. In some embodiments, the subject is taking diazoxide. In some embodiments, the subject is taking diazoxide as dosages as described herein. In some embodiments, a subject is taking diazoxide at dosages within a range of 1 mg/kg/day to 40 mg/kg/day. In some embodiments, a subject is taking diazoxide at dosages within a range of 3 mg/kg/day to 30 mg/kg/day. In some embodiments, a subject is taking diazoxide at dosages within a range of 5 mg/kg/day to 20 mg/kg/day. In some embodiments, the subject is taking diazoxide to control blood glucose levels. In some embodiments, the subject is taking diazoxide to control blood glucose levels with a target level. In some embodiments, the target glucose levels comprise 70-200 mg (milligram )/dL (deciliter). In some embodiments, the target glucose levels comprise 100-190 mg/dL. In some embodiments, the target glucose levels comprise 120-180 mg/dL.

[0112] The method of treating a subject can restore the relative abundance of total glycogen in the subject by administering a therapeutically effective amount of a biologically active sugar. The method of treating a subject can restore the relative abundance of total glycogen in the subject by administering a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by increasing the amount of total glycogen in the subject. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by increasing the amount of total glycogen in the subject. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by increasingthe amount of total glycogen in the subject as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by increasingthe amount of total glycogen in the subject as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. In some embodiments, the relative abundance of total glycogen is restored in the brain of a subject.

[0113] The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by about 5% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by about 10% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by about 15% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by about 20% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by about 25% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by about 30% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by about 35% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by about 40% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by about 45% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by about 50% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by about 55% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by about 60% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by about 65% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by about 70% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by about 75% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by about 80% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by about 85% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by about 90% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by about 95% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar.

[0114] The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by at least 5% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by at least 10% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by at least 15% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by at least 20% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by at least 25% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by at least 30% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by at least 35% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by at least 40% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by at least 45% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by at least 50% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by at least 55% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by at least 60% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by at least 65% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by at least 70% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by at least 75% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by at least 80% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by at least 85% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by at least 90% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by at least 95% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar.

[0115] The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by greater than 5% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by greater than 10% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by greater than 15% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by greater than 20% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by greater than 25% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by greater than 30% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by greater than 35% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by greater than 40% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by greater than 45% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by greater than 50% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by greater than 55% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by greater than 60% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by greater than 65% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by greater than 70% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by greater than 75% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by greater than 80% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by greater than 85% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by greater than 90% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycogen in the subject by greater than 95% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar.

[0116] The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by about 5% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by about 10% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by about 15% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by about 20% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by about 25% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L- fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by about 30% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by about 35% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by about 40% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by about 45% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by about 50% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L- fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by about 55% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by about 60% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by about 65% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by about 70% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by about 75% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L- fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by about 80% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by about 85% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by about 90% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by about 95% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose.

[0117] The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by at least 5% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by atleast 10% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by at least 15% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by at least 20% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by at least 25% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L- fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by at least 30% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by atleast 35% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by at least 40% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by at least 45% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by at least 50% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L- fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by at least 55% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by atleast 60% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by at least 65% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by at least 70% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by at least 75% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L- fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by at least 80% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by atleast 85% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by at least 90% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by at least 95% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose.

[0118] The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by greater than 5% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by greater than 10% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by greater than 15% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by greater than 20% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by greater than 25% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by greater than 30% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by greater than 35% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L- fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by greater than 40% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by greaterthan 45% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by greaterthan 50% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by greater than 55% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by greater than 60% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by greater than 65% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by greaterthan 70% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L- fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by greater than 75% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by greaterthan 80% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by greater than 85% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by greater than 90% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycogen in the subject by greater than 95% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose.

[0119] The method of treating a subject can restore the relative abundance of total glycans in the subject by administering a therapeutically effective amount of a biologically active sugar. The method of treating a subject can restore the relative abundance of total glycans in the subject by administering a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by increasing the amount of total glycans in the subject. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by increasing the amount of total glycans in the subject. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by increasing the amount of total glycans in the subject as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by increasing the amount of total glycans in the subject as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. In some embodiments, the relative abundance of total glycans is restored in the brain of a subject.

[0120] The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by about 5% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by about 10% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by about 15% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by about 20% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by about 25% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by about 30% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by about 35% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by about 40% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by about 45% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by about 50% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by about 55% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by about 60% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by about 65% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by about 70% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by about 75% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by about 80% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by about 85% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by about 90% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by about 95% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar.

[0121] The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by at least 5% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by at least 10% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance oftotal glycans in the subjectby atleast 15% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subjectby atleast 20% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by at least 25% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by at least 30% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance oftotal glycans in the subjectby atleast 35% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subjectby atleast 40% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by at least 45% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by at least 50% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subjectby atleast 55% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by atleast 60% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by at least 65% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by at least 70% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance oftotal glycans in the subjectby atleast 75% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subjectby atleast 80% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by at least 85% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by at least 90% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance oftotal glycans in the subjectby atleast 95% as comparedto a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar.

[0122] The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by greater than 5% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by greater than 10% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by greater than 15% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by greater than 20% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by greater than 25% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by greater than 30% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by greater than 35% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by greater than 40% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by greater than 45% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by greater than 50% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by greaterthan 55% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by greater than 60% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by greater than 65% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by greaterthan 70% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by greater than 75% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by greater than 80% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by greaterthan 85% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by greater than 90% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the relative abundance of total glycans in the subject by greater than 95% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. [0123] The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by about 5% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by about 10% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by about 15% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by about 20% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by about 25% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L- fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by about 30% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by about 35% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by about 40% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by about 45% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by about 50% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L- fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by about 55% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by about 60% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by about 65% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by about 70% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by about 75% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L- fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by about 80% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by about 85% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by about 90% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by about 95% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose.

[0124] The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by at least 5% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by atleast 10% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by at least 15% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by at least 20% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by at least 25% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L- fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by at least 30% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by atleast 35% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by at least 40% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by at least 45% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by at least 50% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L- fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by at least 55% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by atleast 60% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by at least 65% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by at least 70% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by at least 75% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L- fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by at least 80% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by atleast 85% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by at least 90% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by at least 95% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose.

[0125] The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by greater than 5% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by greater than 10% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by greater than 15% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by greater than 20% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by greater than 25% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by greater than 30% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by greater than 35% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L- fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by greater than 40% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by greaterthan 45% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by greater than 50% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by greater than 55% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by greater than 60% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by greaterthan 65% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by greater than 70% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L- fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by greater than 75% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by greater than 80% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by greater than 85% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by greater than 90% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the relative abundance of total glycans in the subject by greater than 95% as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose.

[0126] The method of treating a subject as described herein can restore the chain length distribution of glycogen in the subject by administering a therapeutically effective amount of a biologically active sugar. The method of treating a subject as described herein can restore the chain length distribution of glycogen in the subject by administering a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the chain length distribution of glycogen in the subject by increasing the chain length distribution of glycogen in the subject. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the chain length distribution of glycogen in the subject by increasing the chain length distribution of glycogen in the subject. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the chain length distribution of glycogen in the subject by increasing the amount of the chain length distribution of glycogen in the subject as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the chain length distribution of glycogen in the subject by increasing the amount of the chain length distribution of glycogen in the subject as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. In some embodiments, the chain length distribution of glycogen is restored in the brain of a subject.

[0127] The method of treating a subject as described herein can restore the chain length distribution of glycans in the subject by administering a therapeutically effective amount of a biologically active sugar. The method of treating a subject as described herein can restore the chain length distribution of glycans in the subject by administering a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the chain length distribution of glycans in the subject by increasingthe chain length distribution of glycans in the subject. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the chain length distribution of glycans in the subject by increasing the chain length distribution of glycans in the subject. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the chain length distribution of glycans in the subject by increasingthe amount of the chain length distribution of glycans in the subject as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the chain length distribution of glycans in the subject by increasingthe amount of the chain length distribution of glycans in the subject as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose. In some embodiments, the chain length distribution of glycans is restored in the brain of a subject.

[0128] The method of treating a subject as described herein can restore the gait of the subject by administering a therapeutically effective amount of a biologically active sugar. The method of treating a subject as described herein can restore the gait of the subject by administering a therapeutically effective amount of L-fucose. The method of treating a subject with a therapeutically effective amount of a biologically active sugar can restore the gait of the subject as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of a biologically active sugar. The method of treating a subject with a therapeutically effective amount of L-fucose can restore the gait of the subject as compared to a subject with a disease, condition, or disorder as disclosed herein that is not administered a therapeutically effective amount of L-fucose.

Administration [0129] The methods described herein can comprise administering a therapeutically effective dose of a biologically active sugar to a subject once a day. The methods described herein can comprise administering a therapeutically effective dose of a biologically active sugar orally to a subject once a day. The methods described herein can comprise administering a therapeutically effective dose of L-fucose to a subject once a day. The methods described herein can comprise administering a therapeutically effective dose of L-fucose orally to a subject once a day. The methods described herein can comprise administering a therapeutically effective dose of a biologically active sugar and another biologically active compound to a subject once a day. The methods described herein can comprise administering a therapeutically effective dose of a biologically active sugar and another biologically active compound orally to a subject once a day. The methods described herein can comprise administering a therapeutically effective dose of L- fucose and another biologically active compound to a subject once a day. The methods described herein can comprise administering a therapeutically effective dose of L-fucose and another biologically active compound orally to a subject once a day. The methods described herein can comprise administering a therapeutically effective dose of L-fucose and diazoxide to a subject once a day. The methods described herein can comprise administering a therapeutically effective dose of L-fucose and diazoxide orally to a subject once a day. The methods described herein can comprise administering a therapeutically effective dose of L-fucose and trehalose to a subject once a day. The methods described herein can comprise administering a therapeutically effective dose of L-fucose and trehalose orally to a subject once a day.

[0130] The methods described herein can comprise administering a therapeutically effective dose of a biologically active sugar to a subject at least once a day. The methods described herein can comprise administering a therapeutically effective dose of a biologically active sugar orally to a subject at least once a day. The methods described herein can comprise administering a therapeutically effective dose of L-fucose to a subject at least once a day. The methods described herein can comprise administering a therapeutically effective dose of L-fucose orally to a subject at least once a day. The methods described herein can comprise administering a therapeutically effective dose of a biologically active sugar and another biologically active compound to a subject at least once a day. The methods described herein can comprise administering a therapeutically effective dose of a biologically active sugar and another b iologically active compound orally to a subject at least once a day. The methods described herein can comprise administering a therapeutically effective dose of L-fucose and another biologically active compound to a subject at least once a day. The methods described herein can comprise administering a therapeutically effective dose of L-fucose and another biologically active compound orally to a subject at least once a day. The methods described herein can comprise administering a therapeutically effective dose of L-fucose and diazoxide to a subject at least once a day. The methods described herein can comprise administering a therapeutically effective dose of L-fucose and diazoxide orally to a subject at least once a day. The methods described herein can comprise administering a therapeutically effective dose of L-fucose and trehalose to a subject at least once a day. The methods described herein can comprise administering a therapeutically effective dose of L-fucose and trehalose orally to a subject at least once a day.

[0131] The compounds of the present disclosure can be administered at any suitable frequency, interval and duration. For example, the compound of the present disclosure can be administered once an hour, or two, three or more times an hour, once a day, or two, three, or more times per day, or once every 2, 3, 4, 5, 6, or 7 days, so as to provide the preferred dosage level. When the compound of the present disclosure is administered more than once a day, representative intervals include 5, 10, 15, 20, 30, 45 and 60 minutes, as well as 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 hours. The compound of the present disclosure can be administered once, twice, or three or more times, for an hour, for 1 to 6 hours, for 1 to 12 hours, for 1 to 24 hours, for 6 to 12 hours, for 12 to 24 hours, for a single day, for 1 to 7 days, for a single week, for 1 to 4 weeks, for a month, for 1 to 12 months, for a year or more, or even indefinitely.

[0132] The compounds described herein can be used in combination with one another, or with adjunctive agents that may not be effective alone but may contribute to the efficacy of the active agent. The compounds of the present disclosure can be co-administered with another active agent. Co-administration includes administering the compound of the present disclosure and active agent within 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20, or 24 hours of each other. Co-administration also includes administering the compound of the present disclosure and active agent simultaneously, approximately simultaneously (e.g., within about 1, 5, 10, 15, 20, or 30 minutes of each other), or sequentially in any order. Moreover, the compound of the present disclosure and the active agent can each be administered once a day, or two, three, or more times per day so as to provide the preferred dosage level per day.

[0133] The compound of the present disclosure and the active agent can be present in the compositions of the present disclosure in any suitable weight ratio, such as from about 1 TOO to about 100:1 (w/w), or about 1 :50 to about 50:1, or about 1 :25 to about 25 :1, or about 1 :10 to about 10: 1, or about 1 :5 to about 5 :1 (w/w). The compound of the present disclosure and the other active agent can be present in any suitable weight ratio, such as about 1 TOO (w/w), 1 :50, 1 :25, 1 :10, 1 :5, 1 :4, 1 :3, 1 :2, 1 :1, 2:1, 3 :1, 4: 1, 5: 1, 10: 1, 25 :1, 50:1 or 100: 1 (w/w). Other dosages and dosage ratios of the compound of the present disclosure and the active agent are suitable in the compositions and methods of the present disclosure. [0134] The compounds and compositions of the present disclosure can be delivered by any suitable means, including oral, parenteral and topical methods. Transdermal administration methods, by a topical route, can be formulated as applicator sticks, solutions, suspensions, emulsions, gels, creams, ointments, pastes, jellies, paints, powders, and aerosols. The pharmaceutical preparation is preferably in unit dosage form. In such form the preparation is subdivided into unit doses containing appropriate quantities of the compounds and compositions of the present disclosure. The unit dosage form can be a packaged preparation, the package containing discrete quantities of preparation, such as packeted tablets, capsules, and powders in vials or ampoules. Also, the unit dosage form can be a capsule, tablet, cachet, or lozenge itself, or it can be the appropriate number of any of these in packaged form.

[0135] The pharmaceutical compositions disclosed herein can be administered by ingestion by the subject. The pharmaceutical compositions disclosed herein can also be administered by injection, that is, intravenously, intramuscularly, intracutaneously, subcutaneously, intraduodenally, or intraperitoneally. Also, the pharmaceutical compositions described herein can be administered by inhalation, for example, intranasally. Additionally, the pharmaceutical compositions disclosed herein can be administered transdermally. The pharmaceutical compositions described herein can also be administered by intraocular, intravaginal, and intrarectal routes including suppositories, insufflation, powders and aerosol formulations . The compositions of the present disclosure can also be delivered as microspheres for slow release in the body. For example, microspheres can be formulated for administration via intradermal injection of drug-containing microspheres, which slowly release subcutaneously .

Diseases, Conditions, and Disorders

[0136] In some embodiments, the compositions and methods of the present disclosure are useful for treating a subject with a disease, condition, or disorder, such as a neurological disease, condition, or disorder or a neurodegenerative disease, condition, or disorder.

[0137] In some cases, a neurological disease, condition, or disorder comprises a neurological or neurodegenerative disease, condition, or disorder. The neurological or neurodegenerative disease, condition, or disorder can comprise a neurological or neurodegenerative disease, condition, or disorder associated with a mutation in a gene encoding a solute carrier (SLC) protein. In some cases, the mutation in the gene encoding a solute carrier (SLC) protein is a mutation of a gene encoding a family 2 or family 5 solute carrier (SLC) protein. In some cases, the mutation in the gene encoding a family 2 or family 5 solute carrier (SLC) protein is a mutation of a gene encoding a neutral monosaccharide transporter. In some cases, the neutral monosaccharide transporter is a glucose transporter. In some cases, the mutation in gene encoding a neutral monosaccharide transporter is a mutation of a gene encoding a glucose transporter. In some cases, the mutation in the gene encoding a solute carrier (SLC) family 2 is a mutation of a gene encoding a GLUT protein. In some cases, the mutation in the gene encoding a solute carrier (SLC) family 2 is a mutation of a gene encoding SLC2 member Al (SLC2A1). In some cases, the mutation in the gene encoding SLC2A1 is a mutation of a gene encoding a GLUT protein. In some cases, the mutation in the gene encoding SLC2A1 is a mutation of a gene encoding a GLUT1 protein. In some cases, the mutation in the gene encoding a GLUT protein is a mutation of a gene encoding a class 1 GLUT protein. In some cases, the neurological or neurodegenerative disease or disorder comprises a glycosylation disorder. In some cases, the neurological or neurodegenerative disease or disorder comprises a congenital glycosylation disorder. In some cases, the neurological or neurodegenerative disease or disorder comprises GLUT 1 deficiency syndrome. In some cases, the neurological or neurodegenerative disease or disorder comprises GLUT 1 deficiency syndrome 1 . In some cases, the neurological or neurodegenerative disease or disorder comprises GLUT 1 deficiency syndrome 2. In some cases, the neurological or neurodegenerative disease or disorder comprises a congenital disorder. In some cases, the neurological or neurodegenerative disease or disorder comprises an autosomal dominant disorder.

[0138] In some embodiments, the neurological or neurodegenerative disease or disorder can be associated with seizures. In some embodiments, the neurological or neurodegenerative disease or disorder can be associated with absence seizures. In some embodiments, the neurological or neurodegenerative disease or disorder can be associated with decreased muscle tone. In some embodiments, the neurological or neurodegenerative disease or disorder can be associated with intellectual disability. In some embodiments, the neurological or neurodegenerative disease or disorder can be associated with developmental delays. In some embodiments, the neurological or neurodegenerative disease or disorder can be associated with ataxia. In some embodiments, the neurological or neurodegenerative disease or disorder can be associated with a speech disorder. [0139] In some embodiments, the neurological or neurodegenerative disease or disorder can be associated with reduced glucose uptake. In some embodiments, the neurological or neurodegenerative disease or disorder can be associated with reduced glucose in the cerebral spinal fluid (CSF). In some embodiments, the neurological or neurodegenerative disease or disorder can be associated with reduced total glycogen. In some embodiments, the neurological or neurodegenerative disease or disorder can be associated with reduced glycogen chain length. In some embodiments, the neurological or neurodegenerative disease or disorder can be associated with reduced total glycans.

Subjects [0140] In some aspects, the subject is a mammal. In some aspects, the subject is a human being. In some aspects, the subject is a human patient. In some aspects, the subject can have or is suspected of having a disorder or health condition such as a neurological or neurodegenerative disease or disorder. In some aspects, the subject is healthy. The subject may have a neurological disease, condition, or disorder. The subject may have a neurodegenerative disease, condition, or disorder. The subject may be suspected of having a neurological disease, condition, or disorder. The subject may be suspected ofhaving a neurodegenerative disease, condition, or disorder. The subject may be suspected of having a congenital neurological or neurodegenerative disease, condition, or disorder. The subject may have or be suspected of having a disease, condition, or disorder as disclosed herein.

[0141] The subject can be male. The subject can be female. The subject can be intersex. The gender of the subject can be determined according to the definitions of the American Medical Association (AMA). The subject can be a neonate, infant, child, adolescent, adult or senior according to the definitions of the American Medical Association (AMA). The subject can be a pediatric subject (e.g., a neonate, an infant, a child, or an adolescent) or an adult subject (e.g., a young adult, a middle-aged adult, or a senior adult)). In some embodiments, the subject is an infant, e.g., a human infant. In some embodiments, the infant is a premature infant (e.g., a premature human infant). In some embodiments, the premature infant (e.g., premature human infant) has a gestational age of less than 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, or 27 weeks. In some embodiments, the subject is a child. In some embodiments, the subject is an adolescent. In some embodiments, the subject is an adult. In some embodiments, the subject is less than 20 years of age, less than 19 years of age, less than 18 years of age, less than 17 years of age, less than 16 years of age, less than 15 years of age, or less than 14 years of age, less than 13 years of age, less than 12 years of age, less than 11 years of age, less than 10 years of age, le ss than 9 years of age, less than 8 years of age, less than 7 years of age, less than 6 years of age, less than 5 years of age, less than 4 years of age, less than 3 years of age, less than 2 years of age, or less than 1 year of age. In some embodiments, the subject is less than 14 years of age. In some embodiments, the subject is less than 13 years of age. In some embodiments, the subject is less than 12 years of age. In some embodiments, the subject is less than 11 years of age. In some embodiments, the subject is less than 10 years of age. In some embodiments, the subject is less than 9 years of age. In some embodiments, the subject is less than 8 years of age. In some embodiments, the subject is less than 7 years of age. In some embodiments, the subject is less than 6 years of age. In some embodiments, the subject is less than 5 years of age. In some embodiments, the subject is less than 4 years of age. In some embodiments, the subject is less than 3 years of age. In some embodiments, the subject is less than 2 years of age. In some embodiments, the subject is less than 1 year of age. In some embodiments, the subject is less than 12 months of age. In some embodiments, the subject is less than 11 months of age. In some embodiments, the subject is less than 10 months of age. In some embodiments, the subject is less than 9 months of age. In some embodiments, the subject is less than 8 months of age. In some embodiments, the subject is less than 7 months of age. In some embodiments, the subject is less than 6 months of age. In some embodiments, the subject is less than 5 months of age. In some embodiments, the subject is less than 4 months of age. In some embodiments, the subject is less than 3 months of age. In some embodiments, the subject is less than 2 months of age. In some embodiments, the subject is less than 1 month of age.

[0142] In some embodiments, the subject is not on a specialty diet. In some embodiments, the subject is on a specialty diet. In some embodiments, the subject is on a ketogenic diet. The ketogenic diet can be a classical ketogenic diet. A classical ketogenic diet can comprise consuming 3 grams of fat for every 1 gram of protein and carbohydrates combined (3 :1 ratio) A classical ketogenic can comprise consuming a 4: 1 ratio of fat to protein and carbohydrates combined. The ketogenic diet can be a modified ketogenic diet. A modified ketogenic diet can comprise consuming 2:1 or 1 : 1 ratios of fat to protein and carbohydrates combined. The ketogenic diet can be a modified Atkins Diet. In some embodiments, the subject has experienced a seizure. In some embodiments, the subject has experienced an absence seizure. In some embodiments, the absence seizures are early -onset absence seizures. In some embodiments, the subject has experienced an early -onset absence seizure. In some embodiments, the subject can have epilepsy. In some embodiments, the subject can have reduced glucose uptake.

Additional Enumerated Embodiments

[0143] Embodiment 1 . A method of treating a subject with a neurological or neurodegenerative disease or disorder, the method comprising: administering a therapeutically effective amount of a biologically active sugar to the subject.

[0144] Embodiment 2. A method of treating a subject with a mutation of a gene encoding a family 2 or family 5 solute carrier (SLC) protein, the method comprising: administering a therapeutically effective amount of a biologically active sugar to the subject.

[0145] Embodiment 3. A method of treating a subject with a mutation of a gene encoding a family 2 or 5 solute carrier (SLC) protein, the method comprising: administering a therapeutically effective amount of L-fucose to the subject.

[0146] Embodiment 4. A method of treating a subject with a mutation of a gene encoding a glucose transporter, the method comprising: administering a therapeutically effective amount of a biologically active sugar to the subject. [0147] Embodiment 5. A method of treating a subject with GLUT1 deficiency syndrome, the method comprising: administering a therapeutically effective amount of a biologically active sugar to the subject.

[0148] Embodiment 6. The method of embodiment 1, wherein the neurological or neurodegenerative disease or disorder comprises a mutation in a gene encoding a solute carrier (SLC) protein.

[0149] Embodiment 7. The method of embodiment 4, wherein the glucose transporter gene encodes a solute carrier (SLC) protein.

[0150] Embodiment s. The method of embodiment s, wherein the GLUT1 deficiency syndrome comprises a mutation in a gene encoding a solute carrier (SLC) protein.

[0151] Embodiment 9. The method of any one of embodiments 6-8, wherein the gene encoding the SLC protein is from family 2 (SLC2) or family 5 (SLC5).

[0152] Embodiment 10. The method of any one of the preceding embodiments, wherein the gene encoding the SLC protein is SLC2 member Al (SLC2A1).

[0153] Embodiment 11. The method of any one of the preceding embodiments, wherein the protein encoded by the SLC2A1 gene is glucose transporter 1 (GLUT 1).

[0154] Embodiment 12. The method of any one of the preceding embodiments, wherein the biologically active sugar is a monosaccharide.

[0155] Embodiment 13. The method of any one of the preceding embodiments, wherein the monosaccharide is a neutral monosaccharide.

[0156] Embodiment 14. The method of any one of the preceding embodiments, wherein the neutral monosaccharide is a hexose monosaccharide.

[0157] Embodiment 15. The method of any one of the preceding embodiments, wherein the hexose monosaccharide is a deoxyhexose monosaccharide.

[0158] Embodiment 16. The method of any one of the preceding embodiments, wherein the deoxyhexose monosaccharide is a 6 -deoxyhexose monosaccharide.

[0159] Embodiment 17. The method of any one of the preceding embodiments, wherein the 6- deoxyhexose monosaccharide is in an L-conformation.

[0160] Embodiment 18. The method of any one of the preceding embodiments, wherein the 6- deoxyhexose monosaccharide is fucose.

[0161] Embodiment 19. The method of any one of the preceding embodiments, wherein the fucose is L-fucose.

[0162] Embodiment 20. The method of any one of the preceding embodiments, wherein the method comprises restoring relative abundance of total glycogen in the subject. [0163] Embodiment 21. The method of embodiment 20, wherein restoring the relative abundance of total glycogen in the subject comprises increasing an amount of total glycogen in the subject administered the biologically active sugar about 5% to about 100% as compared to a subject that is not administered the biologically active sugar.

[0164] Embodiment 22. The method of embodiment 20, wherein restoring the relative abundance of total glycogen in the subject comprises increasing an amount of total glycogen in the subject administered the biologically active sugar at least 10%, at least 20%, at least 30%, at least 40%, or at least 50%, as compared to a subject that is not administered the biologically active sugar. [0165] Embodiment 23. The method of embodiment 20, wherein restoring the relative abundance of total glycogen in the subject comprises increasing an amount of total glycogen in the subject administered the biologically active sugar greater than 10%, greater than 20%, greater than 30%, greater than 40%, or greater than 50% as compared to a subject that is not administered the biologically active sugar.

[0166] Embodiment 24. The method of any one of the preceding embodiments, wherein the method comprises restoring chain length distribution of glycogen and glycans in the subject. [0167] Embodiment 25. The method of any one of the preceding embodiments, wherein the method comprises restoring relative abundance of total glycans in the subject.

[0168] Embodiment 26. The method of embodiment 25, wherein restoring the relative abundance of total glycans in the subject comprises increasing an amount of total glycans in the subject administered the biologically active sugar about 5% to about 100% as compared to a subject that is not administered the biologically active sugar.

[0169] Embodiment 27. The method of embodiment 24, wherein restoring the relative abundance of total glycans in the subject comprises increasing an amount of total glycans in the subject administered the biologically active sugar at least 10%, at least 20%, at least 30%, at least 40%, or at least 50%, as compared to a subject that is not administered the biologically active sugar. [0170] Embodiment 28. The method of embodiment 24, wherein restoring the relative abundance of total glycans in the subject comprises increasing an amount of total glycans in the subject administered the biologically active sugar greater than 10%, greater than 20%, greater than 30%, greater than 40%, or greater than 50% as compared to a subject that is not administered the biologically active sugar.

[0171] Embodiment 29. The method of any one of the preceding embodiments, wherein the method comprises restoring gait in the subject.

[0172] Embodiment 30. The method of any one of embodiments 20, 24, or 25, wherein the restoring is in the brain of the subject. [0173] Embodiment s 1. The method of any one of embodiments 20, 24, 25, 29, or 30, wherein the subject has reduced glucose uptake.

[0174] Embodiment 32. The method of any one of the preceding embodiments, wherein the neurological or neurodegenerative disease or disorder comprises GLUT1 deficiency syndrome. [0175] Embodiment 33. The method of any one of the preceding embodiments, wherein the administering comprises delivering the biologically active sugar to the subject via oral, subcutaneous, intravenous, or intraperitoneal administration.

[0176] Embodiment 34. The method of any one of the preceding embodiments, wherein the subject comprises a mammal.

[0177] Embodiment 35. The method of embodiment 34, wherein the subject comprises a human. [0178] While preferred embodiments of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the disclosure. It should be understood that various alternatives to the embodiments of the disclosure described herein may be employed in practicing the disclosure. It is intended that the following claims define the scope of the disclosure and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Examples

[0179] Example 1 — General Experimental procedures used in the seneration of data disclosed herein

[0180] Cell culture: HCT116, HepG2, and Neuro-2a cells (from ATCC) were grown in 1 g/1 glucose Dulbecco’s modified Eagle’s medium (DMEM). DLD-l-WT and DLD-1-GLUT1-KO were maintained in 4.5 g/1 glucose DMEM. All media was supplemented with 10% fetal bovine serum (Sigma-Lot 20J480) and cells grown at 37 C in a humidified incubator at 5% CO2.

[0181] Lectin Staining: The lectin staining was performed as described by Sosicka et al.

(Sosicka, P., Ng, B. G., Pepi, L. E., Shajahan, A., Wong, M., Scott, D. A., et al. (2022) Origin of cytoplasmic GDP-fucose determines its contribu-tion to glycosylation reactions. J. Cell Biol. 221, e202205038). Instead of biotinylated AAL, FITC-labeled AAL (Vector Laboratories), diluted 1 :100, was used.

[0182] Briefly, cells were seeded on 96-well black flat bottom plates (Falconn) with a fresh medium containing increasing concentrations of fucose. Cells were incubated with fucose for another 16 h and analyzed by immunofluorescence staining as described in the next paragraph. [0183] Cells were washed twice with DPBS, incubated for 15 min with 4% paraformaldehyde, washed three times with DPBS, and blocked with Carbo Free Blocking Solution (Vector Laboratories) in DPBS. After 1 h of blocking, FITC-labeled lectins (Vector Laboratories) were diluted in a blocking solution containing 1 mM MgC12, 1 mM CaC12, and 1 mM MnC12 and added for 1 h. aleuria aurantia lectin (AAL) were diluted at 1 : 100, while LTL and UEAI were diluted at 1 : 100. Cells were washed three times with DPBS and incubated for 1 h with Cy3 - labeled streptavidin (Vector Laboratories) diluted 1 : 100 (LTL and UEAI) or 1 : 100 (LCA and AAL) in blocking solution. DAPI (Thermo Fisher Scientific) was then added directly to the solution at a final dilution 1 : 1,000. After 20 min, cells were washed three times in DPBS and 100 pl of DPBS was added to each well, and the plates were sealed with adhesive plate tape (Thermo Fisher Scientific).

[0184] siRNA screen: HCT116 cells were used to screen a panel of 143 siRNA (140 transports, three positive controls) and their effect on AAL staining. The initial screens used a pool of four combined siRNA with each candidate subsequently confirmed using individual siRNA. The lectin staining was performed essentially as described by Sosicka et al., except a 384-well format was used instead of 96-well.

[0185] Inhibition of GLUT1, endocytosis, and macropinocytosis: GLUT1 was inhibited using 100 nMBAY-876 and 150 pMWZB117. Clathrin-dependent endocytosis was inhibited with 36 pM Dynasore. Caveolin-dependent endocytosis was inhibited with 4 mM methyl-3 -cyclodextrin. Macropinocytosis was inhibited with 500 pM amiloride. All inhibitors were purchased from the Cayman Chemical. The toxicity of the inhibitors was assessed for each cell line. Prior to adding L-fucose, cells were preincubated with a respective inhibitor (or their combination) for 1 h. [0186] L-fucose uptake: L-fucose uptake was measured using L-fucose [5,6-³H] (60 Ci/mmol; American Radiolabeled Chemicals, Inc) that was QAE purified. Experiments were performed in serum-free DMEM 1 g/1 glucose medium in 6-well plates. About 10 pCi/ml of radioactive fucose was used in each experiment. About 0.5 ml of the labeling medium was added into each well. Cells were grown in a presence of 5 pM unlabeled L-fucose (Sigma- Aldrich). L-fucose uptake was measured for 1 h. Before collecting cells, they were washed five times with Dulbecco’s phosphate-buffered saline, scraped, and lysed in 2% SDS. Fifty percent of collected material was counted using a scintillation counter. Samples were normalized based on the protein concentration that was assessed with bicinchoninic acid assay method.

[0187] L-fucose and 2-deoxy -D-glucose uptake: To measure an uptake of L-fucose and 2 -deoxy - D-glucose at the same time, cells were grown in serum-free, glucose-free DMEM medium in 6- well plates. About 10 pCi/ml of QAE purified ³H-fucose and 0.8 pCi/ml of 2-deoxy -D-glucose [¹⁴C(U)] (274 mCi/mmol; Perkin Elemer) was used in each experiment. About 0.5 ml of the labeling medium was added into each well. Cells were grown in a presence of 3 pM unlabeled L- fucose, so the concentration of both fucose and 2 -deoxy glucose was the same. Uptake was measured for 2 h. Before collecting cells, they were washed five times with DPBS, scraped, and lysed in 2% SDS. Fifty percent of collected material was counted using a scintillation counter. Samples were normalized based on the protein concentration that was assessed with bicinchoninic acid assay method.

[0188] GC-MS analysis of serum fucose: To measure L-fucose serum concentration 500 pmol of L-[UL-¹³C₆] fucose (Omicron Biochemicals, Inc) was added to 100 pl of serum. To remove glycoproteins, 400 pl of ice-cold acetone was added to each sample and incubated for 16 h, at -20 °C. Next, samples were spun down for 30 min, 4 °C, 14,000 rpm and resulting supernatant was dried in SpeedVac. Samples were dissolved in 200 pl of water, loaded on 3 kDa cutoff filters, and spun down for 15 min, 14,000 rpm, room temperature. Next, additional 200 pl of water was loaded on the filter and samples were spun down again. The flow through the filter was collected and dried in SpeedVac. Finally, the samples were derivatized and analyzed with GC-MS as previously described in Sosicka et al.

[0189] Example 2 — Identification of GLUT1 as a L-fucose transporter

[0190] HCT116 cells lack a functional de novo fucosylation pathway, therefore cellular fucosylation in these cells is dependent on exogenous L-fucose. HCT116 cells were used to screen an siRNA library of approximately 140 genes (140 transporters and three positive controls) to identify a potential L-fucose transporter (FIG. 1A). The fucose-specific lectin, aleuria aurantia lectin (AAL) was used for the screen. AAL recognizes al, 2, al, 3, al, 4 (antennae), and al, 6 (core) linked fucose to visualize fucosylation. After optimizing fucose concentration and time (20 pM for 16 h), the screen was performed at 24 and 48 h post siRNA transfection (FIG. IB). siRNA knockdown of three positive controls, FCSK, FPGT, and SLC35C1, all showed a significant reduction in AAL reactivity (FIG. 1C). This reduction in these positive controls was used to establish the threshold for potential transporter candidates. Only two candidates had comparable reduction in AAL reactivity; GLUT1 was prioritized because it is a well-established, verified monosaccharide transporter (FIG. 1C). The other candidate from the screen was SLCO4A1, which is annotated to encode for a Na⁺-independent transporter of organic anions (FIG. 1C).

[0191] Example 3 — Chemical inhibition of Glutl function blocks L-fucose uptake

[0192] GLUT1 was inhibited usingBAY-876, a potent, highly selective, cell-permeable GLUT1 inhibitor, and WZB117. At 20 nM BAY-876, it reduced D-glucose uptake by 70%, while also reducing L-Fucose uptake by ~50% (FIG. 2A). Increasing the concentration of BAY-876 from 20 nM to 100 nM or 400 nM did not provide a significant reduction in L-fucose uptake but completely blocked D-glucose uptake (FIG. 2A). This effect is comparable to the GLUT1 pooled siRNA used in the screen. The effects of another GLUT1 inhibitor, WZB117, were also tested, showing a similar inhibitory trend (FIG. 2B). Interestingly, the inhibitory effect of BAY-876 could be overcome by increasing the concentration of exogenous L-fucose above 25 pM, suggesting a GLUT 1 -independent mode of entry at higher L-fucose concentrations (FIG. 2A). [0193] Example 4 — Inhibition of maicropinocytosis affects L-fucose uptake

[0194] Amiloride (an inhibitor of macropinocytosis) with a nontoxic concentration (<500 pM) was effective in reducing L-fucose uptake in a dose-dependent manner. The combination of BAY-876 with amiloride was additive (FIG. 2C and FIG. 2D). Neither dynasore, which inhibits clathrin-dependent endocytosis, nor methyl-P-cyclodextrin, which inhibits caveolin-dependent endocytosis, affected L-fucose uptake in either the lectin -based assay or ³H-L-fucose uptake (FIG. 2E, FIG. 2F, and FIG. 3A).

[0195] Example 5 — D-glucose does not affect L-fucose uptake

[0196] In HCT116 cells, increasing concentrations of D-glucose even to hyperphy siological levels had a negligible effect on ³H-L-fucose uptake (FIG. 3B upper panel), suggesting that GLUT1 -dependent D-glucose transport does not compete with L-fucose uptake. However, in HepG2 cells, which have a functional de novo biosynthetic pathway, there was an affect at higher D-glucose concentrations, but this is likely due to nonphy siological glucose flux through the fucose de novo pathway diluting of ³H-L-fucose-GDP pools with unlabeled glucose-derived GDP-fucose (FIG. 3B lower panel). As expected, L-glucose, which is not utilized by mammalian cells, has no effect and serves as a control (FIG. 3C upper and lower panel). [0197] Example 6 — GLUT1 KO cells have diminished L-fucose uptake

[0198] DLD-1 WT and DLD-1 GLUT1 KO colorectal cancer cells (protein expression verified in FIG. 4A) were simultaneously labeled with 3 pM each of 3H-L-fucose and 14C-2 -deoxy -D- glucose to determine the contribution of GLUT1 to their uptake. When compared to WT cells, GLUT1 KO cells had reduced (~50%), but not completely absent uptake of ¹⁴C-2-deoxy-D- glucose (FIG. 4B Right panel), proving there are other transporters for D-glucose. These same KO cells also showed a ~60% reduction in ³H-L-fucose uptake compared to WT cells (FIG. 4B Left panel). These reductions were phenocopied on both ¹⁴C-2-deoxy-D-glucose and ³H-L- fucose by treating WT cells with BAY-876 (FIG. 4B Right and left panel). Amiloride had no effect on ¹⁴C-2-deoxy-D-glucose, while inhibiting ~50% of ³H-L-fucose (FIG. 4B Right and left panel). Treating GLUT1 KO cells with BAY-876 alone had a marginal effect on either ¹⁴C- 2-deoxy -D-glucose or ³H-L-fucose uptake (FIG. 4B Right and left panel). However, there was still 40% to 50% uptake of both, supporting the existence of other, likely transporter -mediated, pathways.

[0199] To determine whether GLUT1 prefers D-glucose or L-fucose transport at low micromolar levels, ³H-L-fucose and ¹⁴C-2 -deoxy -D-glucose uptake (pmol/mg protein) were simultaneously measured in several cell lines. Under these conditions, GLUT1 showed 2- to 3 -fold higher preference for glucose except in the hepatocellular carcinoma line HepG2, where the preference was reversed (FIG. 4C). In contrast, in the absence or presence of 50 pM fucose, the uptake of ¹⁴C-2 -deoxy -D-glucose was not affected and GLUTI showed a higher amount of uptake even in the presence Fucose (FIG. 4D).

[0200] Example 7 — Determination of human serum L-fucose concentrations

[0201] To measure L-fucose serum concentration we spiked in 500 pmol of L-[UL-¹³Ce] fucose (Omicron Biochemicals, Inc) to 100 pl of serum. To remove glycoproteins, we first added 400 pl of ice-cold acetone to each sample and incubated them for 16 hours at -20 °C. Next, samples were spun down for 30 min, 4 °C, 14,000 rpm andresulting supernatant was dried in SpeedVac. Samples were dissolved in 200 pl of water, loaded on 3 kDa cutoff filters, and spun down for 15 min, 14,000 rpm, room temperature. Next, additional 200 pl of water was loaded on the filter and samples were spun down again. The flow through the filter was collected and dried in SpeedVac. Finally, the samples were derivatized and analyzed with GC-MS.

[0202] It has been shown oral L-fucose treatment with 50 to 100 mg/kg body weight can raise serum L-fucose levels to 110 to 210 pmol/1 (Marquardt T., Luhn K., Srikrishna G., Freeze H.H., Harms E., Vestweber D. Correction of leukocyte adhesion deficiency type II with oral fucose. Blood. 1999;94:3976-3985). Prior studies utilized coupled enzymatic assays to determine L-fucose concentrations in various conditions including cancer that in the healthy group ranged from 6 pM to over 500 pM (Sharma M., Sharma E., Prabhu V., Pai V.R., D'Souza J M., Harish S., et al. Salivary L-fucose as a biomarker for oral potentially malignant disorders and oral cancer. J. Cancer Res. Ther. 2020;16:546-550 andManchil P.R., Joy E.T., Kiran M.S., Sherubin J.E., Khan M.F., Aravind B.S. Correlation of serum levo-fucose levels as a biomarker with tumor node metastasis staging in oral cancer patients. J. Pharm. Bioallied Sci. 2016;8:S147-S150).

Given the apparently low pM preference of GLUTI for L-fucose, we next determined the serum concentrations for 23 unrelated individuals using a validated GC-MS method that allowed us to segregate L-fucose from other monosaccharides (Sosicka P., Ng B.G., Pepi L.E., Shajahan A., Wong M., Scott D. A., et al. Origin of cytoplasmic GDP-fucose determines its contribution to glycosylation reactions. J. Cell Biol. 2022;221). We show that the average range is near 1.65 pM (FIG. 5)

[0203] Example 8 — MADLI-MS and Gait Measurements in WT and GLUTI deficient Mice [0204] GLUTI deficient and WT mice were administered L-fucose via oral gavage at 0.2 mg/g of body weight once per day for a period of 10 days. Following the 10-day administration period, MALDI-MS imaging of the brains of the mice revealed defects in brain glycogen (FIG. 6A- FIG. 6C) and glycans (FIG. 7A and FIG. 7B) in the GLUTI deficient mice compared to the WT mice, however 10-day administration of L-fucose was able to reverse this result. Gait was also measured by calculating the average right-side stride angle in WT and GLUT1 deficient mice administered L-fucose (FIG. 8A- FIG. 8C). L-Fucose administration was able to correct the stride of GLUT1 deficient mice such that the stride angle resembled that of a WT mouse (FIG. 8C.). Gait in mice can also be assessed according to the protocol disclosed in Fouda et al. (Fouda R., Argueta D., O'Daniel K., Peterson K., Sorto T., Gupta K. Assessment of gait in mice using simplified analysis tools. Research Square. Protocol Exchange. 05 May 2023. doi.org/10.21203/rs.3.pex-2191/vl).

[0205] Example 9 - Use of L-fucose in an early childhood patient with classical GLUT1 DS

[0206] GLUT1 DS (Deficiency Syndrome) in individuals typically manifests in two phenotypes : classic GLUT1 DS and non-classic GLUT1 DS. The classic form of GLUT1 DS affects about 90% of individuals and usually presents with a history of seizures, typically before the age of 2. [0207] To evaluate the potential of L-fucose to improve the condition of patients with classic GLUT1 DS, patients (aged <3) with GLUT1 DS defined by a low cerebrospinal fluid -to-blood glucose ratio and SLC2A1 mutations are enrolled for L-fucose treatment. Prior to treatment, all patients are on a normal diet, as either they object to or cannot tolerate ketogenic diets.

[0208] The treatment is divided into four phases, each lasting 3 months. During the treatment phase, each patient receives about 20 mg/kgbody weight of L-fucose orally per day, divided into 3-4 doses during meals. A trained dietician determines the patient’s caloric intake and adjusts their daily menu to ensure their diet remains isocaloric when L-fucose is introduced. Baseline evaluations of seizures, neurological development, dysarthria, and movement disorders are conducted before the treatment begins.

[0209] At the end of each treatment phase, symptoms are assessed. Briefly, to assess seizure activity, EEG is used to monitor brain activity and identify seizure patterns. Caregivers are required to maintain detailed diaries of seizure activity, including times, triggers, and durations. Developmental milestones are assessed using standardized tests. In some instances, the Bayley Scales of Infant and Toddler Development are used to assess cognitive, motor, and social - emotional development. Fine and gross motor skills are measured by a pediatric neurologist.

Speech and language development is assessed by a speech-language pathologist to evaluate the patient’s levels compared to age-matched peers.

[0210] We hypothesize that the frequency of seizure decreases after a single phase of treatment. Furthermore, we hypothesize that scaled scores and percentile ranks for cognitive, language, motor, social-emotional, and adaptive behavior improve after two or three phases of treatment. [0211] Example 10 — Use of L-fucose and diazoxide in patient with non-classical GLUT1 DS [0212] Among patients with GLUT1 deficiency syndrome (GLUT1 DS), approximately 10% exhibit a non-classical form, characterized by atypical or milder neurological symptoms without clinical seizures. Non-classical GLUT1 DS includes a broader spectrum of symptoms, which may present later in childhood or adolescence.

[0213] In this study, the ability of L-fucose to improve the condition of patients with non- classical GLUT1 DS is evaluated. Patients (aged >14) with GLUT1 DS defined by a low cerebrospinal fluid-to-blood glucose ratio and SLC2A1 mutations are enrolled for L-fucose treatment. Prior to treatment, all patients are on a normal diet, as either they object to or cannot tolerate ketogenic diets.

[0214] The treatment is divided into four phases, each lasting 3 months. Patients are assigned to one of two groups. During the treatment phase, one group receives about 20 mg/kg body weight of L-fucose orally per day, divided into 3 -4 doses during meals. The other group receives both about 20 mg/kg of L-fucose and about 5 to about 9 mg/kg of diazoxide orally per day, divided into 3-4 doses during meals. For patients receiving L-fucose and diazoxide, blood glucose levels are monitored, typically using continuous glucose monitoring (CGM), to adjust the dosage of diazoxide. The target blood glucose range is 120-180 mg/dL. A trained dietician determines the patient’s caloric intake and adjusts their daily menu to ensure their diet remains isocaloric when L-fucose is introduced. Baseline evaluations of seizures, cognitive and developmental function, and movement disorders are recorded before treatment.

[0215] During each phase, patients and/or their legal guardians are required to complete a comprehensive diary documenting motor (such as absence seizures, abnormal movements, body stiffness, weakness, and speech abnormalities) and non-motor (such as migraine, mood swings) paroxysmal events. These diaries are reviewed by a physician.

[0216] At the end of each treatment phase, seizures, cognitive and developmental function, and movement disorders are reassessed. Electroencephalograms (EEGs) are used to monitor brain activity and identify seizure patterns. Neurological tests are conducted to assess intellectual functioning, language development, and learning abilities. In some cases, behavioral and observational assessments are used to evaluate intellectual functioning. IQ tests are administered to assess cognitive abilities. A basic motor exam is conducted to assess general motor function. In some cases, the timed up-and-go (TUG) test is used to evaluate gait. The dysdiadochokinesia test is used to assess motor coordination. Patients are also assessed using the 6 -minute walk test (6MWT), the nine-hole peg test (9 HPT), and the Clinical Global Impression-Improvement (CGL I) scale.

[0217] We hypothesize that the frequency of absence seizures decreases after one phase of treatment. After 2-3 treatment phases, we expect observable improvements in problem -solving skills, mental flexibility, and overall cognitive function. We also expect an enhancement in intellectual function, reflected in increased IQ scores and a positive shift in percentile ranks across cognitive domains. We also hypothesize that paroxysmal manifestations will decrease throughout the treatment phases.

[0218] While preferred embodiments of the present disclosure have been shown and described herein, it will be understood by those skilled in the art that such embodiments are provided by way of example only. It is not intended that the invention be limited by the specific examples provided within the specification. While embodiments have been described with reference to the aforementioned specification, the descriptions and illustrations of the embodiments herein are not meantto be construed in a limiting sense. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. Furthermore, it shall be understood that all aspects of the invention are not limited to the specific depictions, configurations or relative proportions set forth herein which depend upon a variety of conditions and variables. It should be understood that various alternatives to the embodiments described herein can be employed in practicing the invention. It is therefore contemplated that the invention shall also cover any such alternatives, modifications, variations or equivalents. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

CLAIMS WHAT IS CLAIMED IS:

1 . A method of treating a subject with a neurological or neurodegenerative disease or disorder, the method comprising: administering a therapeutically effective amount of a biologically active sugar to the subject, wherein the neurological or neurodegenerative disease or disorder comprises a mutation in a gene encoding a solute carrier (SLC) protein and the subject is on a ketogenic diet.

2. A method of treating a subject with a mutation of a gene encoding a family 2 or family 5 solute carrier (SLC) protein, the method comprising: administering a therapeutically effective amount of a biologically active sugar to the subject, wherein the method comprises restoring relative abundance of total glycogen in the subject and comprises restoring relative abundance of total glycans in the subject.

3. A method of treating a subject with a mutation of a gene encoding a family 2 or 5 solute carrier (SLC) protein, the method comprising: administering a therapeutically effective amount of L-fucose to the subject.

4. A method of treating a subject with a mutation of a gene encoding a glucose transporter, the method comprising: administering a therapeutically effective amount of a biologically active sugar to the subject, wherein the glucose transporter gene encodes a solute carrier (SLC) protein, and the subject is less than 14 years old.

5. A method of treating a subject with GLUT1 deficiency syndrome, the method comprising: administering a therapeutically effective amount of a biologically active sugar to the subject at least once a day, wherein the biologically active sugar is L-fucose.

6. The method of claim 1 , wherein the ketogenic diet is a classical ketogenic diet (3 :1 or 4 : 1 ratio)), a modified ketogenic diet (2: 1 or 1 :1 ratios) or a modified Atkins Diet.

7. The method of claim 4, wherein the subject is less than 5 years old.

8. The method of claim 5, wherein the GLUT1 deficiency syndrome comprises a mutation in a gene encoding a solute carrier (SLC) protein.

9. The method of any one of claims 6-8, wherein the gene encodingthe SLC protein is from family 2 (SLC2) or family 5 (SLC5).

10. The method of any one of the preceding claims, wherein the gene encoding the SLC protein is SLC2 member Al (SLC2A1).

11 . The method of any one of the preceding claims, wherein the protein encoded by the SLC2A1 gene is glucose transporter 1 (GLUT 1).

12. The method of any one of claims 1-4, 6, 7 and 9-11, wherein the biologically active sugar is a monosaccharide.

13. The method of claimsl-4, 6, 7 and 9-12, wherein the monosaccharide is a neutral monosaccharide.

14. The method of claims 1-4, 6, 7 and 9-13, wherein the neutral monosaccharide is a hexose monosaccharide.

15. The method of any one of claims 1-4, 6, 7 and 9-14, wherein the hexose monosaccharide is a deoxyhexose monosaccharide.

16. The method of any one of claims 1-4, 6, 7 and 9-15, wherein the deoxyhexose monosaccharide is a 6-deoxyhexose monosaccharide.

17. The method of any one of claims 1-4, 6, 7 and 9-11, wherein the 6-deoxyhexose monosaccharide is in an L-conformation.

18. The method of any one of claims 1-4, 6, 7 and 9-11, wherein the 6-deoxyhexose monosaccharide is L-fucose.

19. The method of any one of the preceding claims, wherein the subject is diagnosed as experiencing at least one seizure prior to treatment.

20. The method of any one of the preceding claims, wherein the method comprises restoring relative abundance of total glycogen in the subject, and wherein restoring the relative abundance of total glycogen in the subject comprises increasing an amount of total glycogen in the subject administered the biologically active sugar about 5% to about 100% as compared to a subject that is not administered the biologically active sugar.

21 . The method of claim 20, wherein restoring the relative abundance of total glycogen in the subject comprises increasing an amount of total glycogen in the subject administered the biologically active sugar 5% to 100% as compared to a subject that is not administered the biologically active sugar.

22. The method of claim 20, wherein restoring the relative abundance of total glycogen in the subject comprises increasing an amount of total glycogen in the subject administered the biologically active sugar at least 10%, at least 20%, at least 30%, at least 40%, or at least 50%, as compared to a subject that is not administered the biologically active sugar.

23. The method of claim 20, wherein restoring the relative abundance of total glycogen in the subject comprises increasing an amount of total glycogen in the subject administered the biologically active sugar greater than 10%, greater than 20%, greater than 30%, greater than 40%, or greater than 50% as compared to a subject that is not administered the biologically active sugar.

24. The method of any one of the preceding claims, wherein the method comprises restoring chain length distribution of glycogen and glycans in the subject.

25. The method of any one of the preceding claims, wherein the method comprises restoring relative abundance of total glycans in the subject, and wherein restoring the relative abundance of total glycans in the subject comprises increasing an amount of total glycans in the subject administered the biologically active sugar about 5% to about 100% as compared to a subject that is not administered the biologically active sugar.

26. The method of claim 25, wherein restoring the relative abundance of total glycans in the subject comprises increasing an amount of total glycans in the subject administered the biologically active sugar 5% to 100% as compared to a subject that is not administered the biologically active sugar.

27. The method of claim 25, wherein restoring the relative abundance of total glycans in the subject comprises increasing an amount of total glycans in the subject administered the biologically active sugar at least 10%, at least 20%, at least 30%, at least 40%, or at least 50%, as compared to a subject that is not administered the biologically active sugar.

28. The method of claim 25, wherein restoringthe relative abundance of total glycans in the subject comprises increasing an amount of total glycans in the subject administered the biologically active sugar greater than 10%, greater than 20%, greater than 30%, greater than 40%, or greater than 50% as compared to a subject that is not administered the biologically active sugar.

29. The method of any one of the preceding claims, wherein the method comprises restoring gait in the subject.

30. The method of any one of claims 20, 24, or 25, wherein the restoringis in the brain of the subject.

31 . The method of any one of claims 20, 24, 25, 29, or 30, wherein the subject has reduced glucose uptake.

32. The method of any one of the preceding claims, wherein the neurological or neurodegenerative disease or disorder comprises GLUT1 deficiency syndrome.

33. The method of any one of the preceding claims, wherein the administering comprises delivering the biologically active sugar to the subject via oral, subcutaneous, intravenous, or intraperitoneal administration.

34. The method of any one of the preceding claims, wherein the subject is a mammal.

35. The method of claim 34, wherein the subject is a human.

36. The method of any one of the preceding claims, further comprising administering diazoxide to the subject.

37. The method of any one of the preceding claims, wherein the subject is taking diazoxide to control blood glucose levels within a target level.

-SO-

38. The method of claim 37, wherein the target level is blood glucoses of 120-180 mg/dL.

39. The method of claim 38, the diazoxide dose is within a range of 5-20 mg/kg/day.

40. The method of any one of the preceding claims, wherein the subject has experienced absence seizures prior to treatment.

41 . The method of claim 40, wherein the absence seizures are early -onset absence seizures.

42. The method of any one of the preceding claims, wherein the subject has epilepsy.

43. The method of any one of the preceding claims, wherein the subject is a neonate, infant, child, adolescent, or adult according to American Medical Associations’ age designations.

44. The method of any one of the preceding claims, wherein the subject is a neonate, infant, child, or adolescent according to American Medical Associations’ age designations.

45. The method of any one of the preceding claims, wherein the subject is a neonate, infant, or child, according to American Medical Associations’ age designations.

46. The method of any one of the preceding claims, wherein the subject is a neonate, or infant according to American Medical Associations’ age designations.

47. The method of any one of the preceding claims, wherein the subject is male, female or intersex according to American Medical Associations’ definitions.

48. The method of claim 47, wherein the subject is male according to American Medical Associations’ definition.

49. The method of claim 47, wherein the subject is female according to American Medical Associations’ definition.

50. The method of claim 47, wherein the subject is intersex according to American Medical Associations’ definition.