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WO2015023132A1 - Composition de traitement et de prévention de la sclérose en plaques - Google Patents

Composition de traitement et de prévention de la sclérose en plaques Download PDF

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Publication number
WO2015023132A1
WO2015023132A1 PCT/KR2014/007545 KR2014007545W WO2015023132A1 WO 2015023132 A1 WO2015023132 A1 WO 2015023132A1 KR 2014007545 W KR2014007545 W KR 2014007545W WO 2015023132 A1 WO2015023132 A1 WO 2015023132A1
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Prior art keywords
peptide
ria
multiple sclerosis
composition
treating
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Ceased
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English (en)
Korean (ko)
Inventor
김상재
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Kael-GemVax Co Ltd
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Kael-GemVax Co Ltd
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Priority to KR1020167003030A priority Critical patent/KR102204476B1/ko
Publication of WO2015023132A1 publication Critical patent/WO2015023132A1/fr
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/10—Peptides having 12 to 20 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof

Definitions

  • the present invention relates to a composition for treating and preventing multiple sclerosis. More specifically, the present invention relates to a composition for treating and preventing multiple sclerosis as a composition comprising a peptide derived from telomerase.
  • Multiple sclerosis is a representative disease of autoimmune inflammatory neurodegenerative disease, which is rare in Asians and Africans, but most frequently in Europeans, especially Caucasian women in their 30s. In Caucasian whites, the frequency affects 200 people per 100,000.
  • Multiple sclerosis involves visual impairment, dysfunction of the limbs and resulting gait disturbances, skin sensation impairment with pain or numbness, defecation and urination disorders, speech and hearing disorders, cognitive impairment, etc. Often it gets worse.
  • This neurological disorder is due to damage to myelin sheaths surrounding the axons of nerve cells due to inflammatory responses in the central nervous system.
  • the lesions are scattered in the white matter areas of the brain and spinal cord. In the lesions, inflammatory reactions involving perivenous inflammatory cell infiltration and bullous myelin sheaths of nerve fibers are observed. In addition, loss and appearance of oligodendrocytes Proliferation of glial cells.
  • Multiple sclerosis is an immunological disease involving both cellular and humoral immune systems, as mentioned earlier, and various immunotherapies have been attempted: 1) desensitization of autoreactive T cells using immuno-tolerant antigens, and 2) T cells. Immunization using monoclonal antibodies or interferon-gamma against directional cytokines, B cell surface molecules or cell adhesion molecules, 3) plasma separation and the like have been attempted. These therapies have positive results, but their use is limited due to undesirable side effects (Steinman & Zamvil, Ann. Neurol. 60: 12-21, 2006). Therefore, the development of a safe drug without side effects and toxicity for patients with multiple sclerosis is urgently needed.
  • the present inventors have completed the present invention as a result of diligent efforts to develop a composition for treating and preventing multiple sclerosis with excellent effects while minimizing side effects.
  • telomerase a peptide derived from telomerase can have an excellent effect in treating and preventing compositions for treating and preventing multiple sclerosis and completed the present invention.
  • An object of the present invention is to provide a composition having an effect on the treatment and prevention of multiple sclerosis treatment and prevention.
  • composition for treating and preventing multiple sclerosis comprising a peptide comprising the amino acid sequence of SEQ ID NO: 1, a peptide having a sequence homology of 80% or more with the amino acid sequence or a fragment thereof.
  • the fragment may be a fragment consisting of three or more amino acids.
  • composition according to one aspect of the present invention may be one containing the peptide at a low dose.
  • composition according to one aspect of the present invention may include the peptide at a concentration of 10 nmol / kg or less.
  • composition according to one aspect of the present invention may be one containing the peptide at a concentration of 5 nmol / kg or less.
  • composition according to one aspect of the present invention may be one containing the peptide at a concentration of 1 nmol / kg or less.
  • composition according to one aspect of the present invention may be one containing the peptide at a concentration of 0.2 nmol / kg or less.
  • composition according to one aspect of the invention may be a pharmaceutical composition.
  • composition according to one aspect of the present invention may be a food composition.
  • the method for treating and preventing multiple sclerosis according to one aspect of the present invention may use a composition comprising a low dose of a peptide.
  • a peptide having a sequence of SEQ ID NO: 1 according to the present invention (hereinafter referred to as peptide "RIA") or a peptide or fragment having a sequence having 80% homology with the sequence is excellent in the treatment and prevention of multiple sclerosis. Has the effect, especially when administered at a low dose has the advantage of showing a good effect.
  • peptide RIA is administered in separate doses by intraperitoneal and subcutaneous injection (experimental day 0) at the induction of experimental autoimmune encephalomyelitis (EAE) (200 days).
  • EAE experimental autoimmune encephalomyelitis
  • FIG. 2 is an experiment to identify an effective dosage route, in which doses of peptide RIA were administered in separate doses by intraperitoneal and subcutaneous injection when EAE symptoms reached peak (day 22) (200 nmol IP, 50 nmol SC) ) Is a graph showing the results.
  • Figure 3 is a graph showing the results of administration of RIA 50nmol / kg, RIA 25nmol / kg, RIA 10nmol / kg during EAE induction (day 0).
  • FIG. 4 is a graph showing the results of administration of peptide RIA after RIA 50nmol / kg, RIA 25nmol / kg, RIA1 0nmol / kg, and RIA 5nmol / kg after symptom onset (day 22).
  • Figure 5 is a graph showing the results of administration of RIA 25nmol / kg, RIA 5nmol / kg, RIA 1nmol / kg, RIA 0.2nmol / kg at EAE induction (day 0).
  • Figure 6 is a graph showing the results of administration of RIA 25nmol, RIA 5nmol, RIA 1nmol, RIA 0.2nmol peptide RIA after the onset of symptoms (day 22).
  • Figure 7 shows drainage lymph nodes after primary antigenic stimulation (myelin oligodendroglial protein, MOG 35-45 ), peptide RIA 1nmol / kg, 0.2nmol / kg and PBS after primary antigenic stimulation It is a graph showing the results of T cell proliferation after in vitro secondary antigenic stimulation to cells isolated from lymph nodes.
  • the present invention may be variously modified and may have various embodiments.
  • the present invention will be described in more detail. However, this is not intended to limit the present invention to specific embodiments, it should be understood to include all transformations, equivalents, and substitutes included in the spirit and scope of the present invention.
  • the detailed description of the related known technology may obscure the gist of the present invention, the detailed description thereof will be omitted.
  • Telomere is a genetic material repeatedly present at the end of a chromosome and is known to prevent damage to the chromosome or binding to another chromosome. Each time a cell divides, the telomeres become slightly shorter. After a certain number of cell divisions, the telomeres become very short, and the cells stop dividing and die. On the other hand, elongation of telomeres is known to prolong cell life. For example, cancer cells secrete an enzyme called telomerase, which prevents telomeres from shortening, so that cancer cells can continue to proliferate without dying. The inventors have confirmed that the peptide derived from telomerase is effective in the treatment and prevention of multiple sclerosis and have completed the present invention.
  • a peptide of SEQ ID NO: 1, a peptide that is a fragment of SEQ ID NO: 1, or a peptide having a sequence homology of at least 80% with the peptide sequence is used in telomerase, specifically in human ( Homo sapiens ) telomerase. Peptides derived.
  • Peptides disclosed herein can include peptides having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% homology.
  • the peptides disclosed herein, peptides or fragments thereof comprising SEQ ID NO: 1 and one or more amino acids, two or more amino acids, three or more amino acids, four or more amino acids, five or more amino acids, six or more amino acids Or peptides with seven or more amino acids changed.
  • amino acid changes belong to a property that allows the physicochemical properties of the peptide to be altered.
  • amino acid changes can be made, such as improving the thermal stability of the peptide, altering substrate specificity, changing the optimal pH, and the like.
  • amino acid includes not only the 22 standard amino acids that are naturally incorporated into the peptide, but also D-isomers and modified amino acids. Accordingly, in one aspect of the invention the peptide may be a peptide comprising D-amino acids. Meanwhile, in another aspect of the present invention, the peptide may include a non-standard amino acid or the like which has been post-translational modified.
  • post-translational modifications include phosphorylation, glycosylation, acylation (including, for example, acetylation, myristoylation and palmitoylation), alkylation ), Carboxylation, hydroxylation, glycation, biotinylation, ubiquitinylation, changes in chemical properties (e.g., beta-elimination deimidization) , Deamidation) and structural changes (eg, formation of disulfide bridges). It also includes changes in amino acids, such as changes in amino groups, carboxy groups or side chains, caused by chemical reactions that occur during the linkage with crosslinkers to form peptide conjugates.
  • Peptides disclosed herein can be wild-type peptides identified and isolated from a natural source.
  • the peptides disclosed herein may be artificial variants, comprising an amino acid sequence in which one or more amino acids are substituted, deleted and / or inserted compared to peptides that are fragments of SEQ ID NO: 1.
  • Amino acid changes in the wild type polypeptide as well as in artificial variants include conservative amino acid substitutions that do not significantly affect the folding and / or activity of the protein.
  • conservative substitutions include basic amino acids (arginine, lysine and histidine), acidic amino acids (glutamic acid and aspartic acid), polar amino acids (glutamine and asparagine), hydrophobic amino acids (leucine, isoleucine, valine and methionine), aromatic amino acids (phenylalanine, Tryptophan and tyrosine), and small amino acids (glycine, alanine, serine and threonine). Amino acid substitutions that generally do not alter specific activity are known in the art.
  • the most common exchanges are Ala / Ser, Val / Ile, Asp / Glu, Thr / Ser, Ala / Gly, Ala / Thr, Ser / Asn, Ala / Val, Ser / Gly, Tyr / Phe, Ala / Pro, Lys / Arg, Asp / Asn, Leu / Ile, Leu / Val, Ala / Glu, and Asp / Gly, and vice versa.
  • Other examples of conservative substitutions are shown in the following table.
  • hydrophobic norleucine, met, ala, val, leu, ile
  • Non-conservative substitutions will be made by exchanging a member of one of these classes for another class. Any cysteine residue that is not involved in maintaining the proper conformation of the peptide can generally be substituted with serine to improve the oxidative stability of the molecule and to prevent abnormal crosslinking. Conversely, cysteine bond (s) can be added to the peptide to improve its stability.
  • Another type of amino acid variant of the peptide is a change in the glycosylation pattern of the antibody.
  • change is meant the deletion of one or more carbohydrate residues found in the peptide and / or the addition of one or more glycosylation sites that are not present in the peptide.
  • N-linked refers to a carbohydrate moiety attached to the side chain of an asparagine moiety.
  • Tripeptide sequences asparagine-X-serine and asparagine-X-threonine, where X is any amino acid except proline, are recognition sequences for enzymatic attachment of carbohydrate moieties to asparagine side chains.
  • O-linked glycosylation means attaching one of the sugars N-acetylgalactosamine, galactose or xylose to hydroxyamino acids, most commonly serine or threonine, but 5-hydroxyproline or 5-hydroxylysine You can also use
  • glycosylation sites to the peptide is conveniently performed by changing the amino acid sequence to contain one or more of the above mentioned tripeptide sequences (for N-linked glycosylation sites). Such changes may also be made by adding or replacing one or more serine or threonine residues with the sequence of the original antibody (for O-linked glycosylation sites).
  • a peptide having a sequence of SEQ ID NO: 1, a peptide which is a fragment of SEQ ID NO: 1, or a peptide having a sequence homology of 80% or more with the peptide sequence according to an aspect of the present invention has low intracellular toxicity and stability in vivo. This has the advantage of being high.
  • SEQ ID NO: 1 in the present invention is a telomerase-derived peptide consisting of 16 amino acids as follows.
  • the composition for treating and preventing multiple sclerosis comprising a peptide comprising an amino acid sequence of SEQ ID NO: 1, a peptide having a sequence homology of 80% or more with the amino acid sequence, or a fragment thereof as an active ingredient.
  • a peptide comprising the amino acid sequence of SEQ ID NO: 1, a peptide having a sequence homology of 80% or more with the amino acid sequence, or a fragment thereof, for use in the treatment or prevention of multiple sclerosis. It may be used for.
  • composition comprising a peptide comprising the amino acid sequence of SEQ ID NO: 1, a peptide having a sequence homology of 80% or more with the amino acid sequence, or a fragment thereof, a composition for treating or preventing multiple sclerosis It may be used for the preparation of.
  • a peptide comprising the amino acid sequence of SEQ ID NO: 1 for use in treating or preventing multiple sclerosis, or for preparing a composition for treating or preventing multiple sclerosis, said amino acid Peptides are peptides or fragments thereof that have at least 80% sequence homology with a sequence.
  • Multiple sclerosis treatment and prophylactic composition comprises a peptide comprising an amino acid sequence of SEQ ID NO: 1 in one aspect, a peptide having a sequence homology of 80% or more with the amino acid sequence or a fragment thereof 0.01g / L to 1kg / L, specifically 0.1g / L to 100 / L, more specifically may be included in the content of 1g / L to 10g / L, but if the difference in effect according to the dose can be appropriately adjusted have.
  • it is not only appropriate to exhibit the intended effect of the present invention, but also satisfies both the stability and safety of the composition it may be appropriate to include in the above range in terms of cost-effectiveness. .
  • composition according to one aspect of the present invention can be applied to all animals including humans, dogs, chickens, pigs, cattle, sheep, guinea pigs or monkeys.
  • the composition comprises a peptide comprising an amino acid sequence of SEQ ID NO: 1, a therapeutic agent for multiple sclerosis comprising a peptide which is a peptide having a sequence homology of 80% or more with the amino acid sequence or a fragment thereof as an active ingredient, and Provided is a prophylactic pharmaceutical composition.
  • the pharmaceutical composition according to one aspect of the present invention may be administered orally, rectal, transdermal, intravenous, intramuscular, intraperitoneal, intramedullary, intradural or subcutaneous.
  • Formulations for oral administration may be, but are not limited to, tablets, pills, soft or hard capsules, granules, powders, solutions or emulsions.
  • Formulations for parenteral administration may be, but are not limited to, injections, drops, lotions, ointments, gels, creams, suspensions, emulsions, suppositories, patches or sprays.
  • compositions according to one aspect of the invention may include additives such as diluents, excipients, lubricants, binders, disintegrants, buffers, dispersants, surfactants, colorants, flavoring or sweetening agents as needed.
  • additives such as diluents, excipients, lubricants, binders, disintegrants, buffers, dispersants, surfactants, colorants, flavoring or sweetening agents as needed.
  • Pharmaceutical compositions according to one aspect of the invention may be prepared by conventional methods in the art.
  • the active ingredient of the pharmaceutical composition according to one aspect of the present invention will vary depending on the age, sex, weight, pathology and severity of the subject to be administered, the route of administration or the judgment of the prescriber.
  • Application dose determination based on these factors is within the level of those skilled in the art, and the single dose thereof may be for example 1 ng / kg to 10 mg / kg, specifically 10 ng / kg to 1 mg / kg, more specifically 0.1 ⁇ g / kg to 100 ⁇ g / kg, more specifically, 0.2 ⁇ g / kg to 20 ⁇ g / kg, but when the difference in effect depending on the dose can be adjusted appropriately.
  • the pharmaceutical composition according to an aspect of the present invention may be administered once to three times a day, but is not limited thereto. When the difference in effect according to the dose is shown, it may be appropriately controlled, and the age of the subject to be administered, It can depend on many factors, including your health and complications.
  • the composition comprises a peptide comprising an amino acid sequence of SEQ ID NO: 1, a therapeutic agent for multiple sclerosis comprising a peptide which is a peptide having a sequence homology of 80% or more with the amino acid sequence or a fragment thereof as an active ingredient, and Provide a prophylactic food composition.
  • the formulation of the food composition according to one aspect of the present invention is not particularly limited, but may be, for example, formulated into tablets, granules, powders, solutions, solid preparations, and the like.
  • Each formulation may be appropriately selected and formulated by those skilled in the art according to the formulation or purpose of use, in addition to the active ingredient, and may be synergistic when applied simultaneously with other raw materials.
  • Preferred embodiments of the invention include the most optimal mode known to the inventors for carrying out the invention. Variations of the preferred embodiments may become apparent to those skilled in the art upon reading the foregoing description. The inventors expect those skilled in the art to make appropriate use of such variations, and the inventors expect the invention to be practiced in a manner different from that described herein. Accordingly, the invention includes all modifications and equivalents of the subject matter referred to in the appended claims, as permitted by patent law. Moreover, any combination of the abovementioned elements within all possible variations is included in the invention unless expressly stated to the contrary or apparently contradictory in context. While the invention has been particularly shown and described with reference to exemplary embodiments, those skilled in the art will understand that various changes in form and detail may be made without departing from the spirit and scope of the invention as defined by the following claims .
  • the EAE mouse model was to determine the effect of preventing and treating multiple sclerosis of peptide RIA.
  • the peptide of SEQ ID NO: 1 (hereinafter referred to as "RIA") was prepared according to the known solid phase peptide synthesis method. Specifically, peptides were synthesized by coupling amino acids one by one from the C-terminus through Fmoc solid phase synthesis (SPPS) using ASP48S (Peptron, Inc., Daejeon, Korea). As follows, the first amino acid at the C-terminus of the peptides was attached to the resin. For example:
  • Coupling reagent is HBTU [2- (1H-Benzotriazole-1-yl) -1,1,3,3-tetamethylaminium hexafluorophosphate] / HOBt [N-Hydroxxybenzotriazole] / NMM [4-Methylmorpholine] It was. Fmoc removal was performed using piperidine in DMF in 20% of DMF.
  • TFA trifluoroacetic acid
  • TIS triisopropylsilane
  • EDT ethanedithiol
  • Each peptide was synthesized by repeating a process of reacting the amino acids with each other, washing with a solvent, and then deprotecting the amino acid using the state in which the amino acid protecting group was bound to the solid support.
  • the synthesized peptide was separated from the resin and then purified by HPLC, and confirmed by MS and lyophilized.
  • an EAE mouse model was used as the animal model of multiple sclerosis. Details on how to build an EAE mouse model as an animal model of multiple sclerosis are known in a number of prior publications (Baker et al., Review article, ACNR, Volume 6, 2007; Kim Dae-seung et al., Korean J Vet Res) , 51 (2), 139-149pp, 2011)
  • Animals used for EAE model construction were used female C57BL / 6 (B6) mice of 6-8 weeks of age.
  • the experimental animals were bred and used at the National Cancer Center's Laboratory Animal Research Center according to the guidelines of the International Association of Laboratory Animal Management, and managed in a specific pathogen free (SPF) environment.
  • SPF pathogen free
  • the EAE mouse model was tested divided into five groups as shown in Table 2 below.
  • the method for preparing an EAE animal model according to the five groups classified above is as follows.
  • 250 ⁇ g of complete Freund's adjuvant (CFA), Mycobacterium tuberculosis H37Ra (Difco, Detroit, MI) 100 ⁇ g and emulsion containing MOG 35-55 peptide were injected subcutaneously, and additionally 200 ng of pertussis toxin (List Biological Laboratories, Campbell, CA) was injected intraperitoneally on day 0 & 2.
  • Control mice were injected with physiological saline only in the same manner as the experimental group.
  • peptide RIA group RIA was injected intraperitoneally (IP) or subcutaneously (SC) at defined doses.
  • mice received the MOG- 45 peptide and scored the symptoms appearing in the mice every day after 10 days.
  • the clinical status of each control group and the experimental group was analyzed and body weight was measured at each reference date.
  • ketamine 1000 mg / kg of ketamine (Ketamin) was injected intraperitoneally for serum collection, and then 1-2 ml of blood was collected by dissecting the rib cage and puncturing the left ventricle. The collected blood was centrifuged at 3000C (3000 rpm, 10 minutes) to separate serum.
  • This single cell suspension was subjected to 10% FBS (Fetal Bovine Serum, Sigma-Aldrich), 1.4 mM glutamine, 20 ⁇ M 2-ME (2-Hydroxyethylmercaptan, Sigma-Aldrich), 100 U / ml penicillin, 100 ⁇ g / ml streptomycin (Life Technologies / RPMI medium containing BRL, Grand Island, NY) was dispensed at 2.5 ⁇ 10 5 cells / well in Roswell Park Memorial Institute medium, Gibco, Eggenstein, Germany.
  • FBS Fetal Bovine Serum, Sigma-Aldrich
  • 2-ME (2-Hydroxyethylmercaptan Sigma-Aldrich
  • 100 U / ml penicillin 100 ⁇ g / ml streptomycin (Life Technologies / RPMI medium containing BRL, Grand Island, NY) was dispensed at 2.5 ⁇ 10 5 cells / well in Roswell Park Memorial Institute medium, Gibco, Eggenstein, Germany.
  • In vitro secondary antigenic (MOG 35-55 ) and non-antigenic (plate-bound anti-CD3 / soluble anti-CD28) stimulation was added to the culture and then incubated at 37 °C, 5% CO 2 / air. The supernatant was removed from the cultured T cells, and the culture solution added with tritium thymidine (3H-thymidine) was added thereto, followed by incubation for 18 hours, and the degree of thymidine incorporation was measured by a gamma-counter.
  • the spinal cord and brain of the mouse were extracted and fixed in 4% paraformaldehyde for 6 hours. Then, paraffin embedded in 30% sucrose was maintained at 4 °C for one day. Hematoxylin and eosin stains were used to evaluate the perivascular leukocyte invasion of the lesions, and Luxol fast blue (LFB) staining was used to evaluate the degree of demyelination of the lesions. Was evaluated.
  • LLB Luxol fast blue
  • Peptide RIA was administered at the appropriate concentration for each route to identify effective route of administration during intraperitoneal injection (IP) and subcutaneous injection (SC).
  • IP intraperitoneal injection
  • SC subcutaneous injection
  • RIA 200nmol RIA 200nmol / kg
  • RIA 50nmol RIA 50nmol / kg
  • the subcutaneous injection group was confirmed to show a similar effect even when administered a low dose of peptide RIA compared to the intraperitoneal injection group, and decided to use only the subcutaneous injection method.
  • RIA 50nmol, RIA 25nmol, and RIA 10nmol were administered at the time of EAE induction (day 0) by subcutaneous injection.
  • EAN symptoms were rapidly expressed at 50nmol / kg and 25nmol / kg for a long time. The results were sustained. However, at 10 nmol / kg, EAE symptoms were late and short-lived, and the intensity of symptoms was low.
  • the myoclonic modality was remarkable, whereas at 10nmol / kg, the myoclonic modality was weak.
  • RIA 50nmol, RIA 25nmol, RIA 10nmol, and RIA 5nmol were administered when EAE symptoms peaked by subcutaneous injection (Day 22), and EAE at 50nmol / kg, 25nmol / kg, and 10nmol / kg. Long-term symptoms were observed, but at 5 nmol / kg, EAE symptoms were rapidly recovered after peptide RIA administration. At 50nmol / kg and 25nmol / kg, the myoclonic modality was remarkable, whereas at 10nmol / kg, the myoclonic modality was weak.
  • RIA 25nmol, RIA 5nmol, RIA 1nmol, and RIA 0.2nmol were administered at the time of EAE induction (day 0) by subcutaneous injection (2 experiments under the same conditions). The symptoms appeared quickly, lasted a long time and were found to be severe.
  • peptide RIA was administered by subcutaneous injection (day 22) after RIA 25nmol, RIA 5nmol, RIA 1nmol, RIA 0.2nmol (2 experiments under the same conditions), EAE at 25nmol / kg Symptoms were observed to last longer than controls. On the other hand, at 5nmol / kg, 1nmol / kg and 0.2nmol / kg, EAE symptoms recovered rapidly after administration of peptide RIA, and the effect was more pronounced at low dose.
  • Example 3 Through the results of Example 3, it was confirmed that EAE symptoms worsen in both aspects of prophylactic treatment and treatment of symptoms when high concentration (10, 25, 50 nmol / kg) peptide RIA was administered, and low concentration (5, 1, 0.2 nmol / kg of peptide RIA showed significant clinical effects in both prophylactic treatment and ongoing disease treatment.
  • peptide RIA can cross the Brain-Brain Barrier (BBB) in the EAE model and act directly on the brains of already inflamed mice.
  • BBB Brain-Brain Barrier
  • administration of the peptide RIA according to the present invention at a low dose (1 nmol / kg, 0.2 nmol / kg) reduces T-cell proliferation, which has a significant effect on the treatment of autoimmune diseases of central nervous system lesions including multiple sclerosis. It can be expected to be developed as a useful drug to treat the disease.
  • the peptide RIA according to the present invention when administered at a low dose, unlike the high-dose administration, it does not show any side effect of myoclonus, but directly affects the central nervous system lesions, which is suitable for acute treatment.
  • T cell proliferation is reduced and shows a significant effect on the treatment of autoimmune diseases, it can be used as a useful drug for the treatment of central nervous system lesions including multiple sclerosis and there is a possibility of further development. .
  • SEQ ID NO 2 Human telomerase full length protein [1-1132aa]

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Abstract

La présente invention concerne une composition de traitement et de prévention de la sclérose en plaques. Plus spécifiquement, la présente invention concerne une composition qui contient un peptide dérivé de télomérase et qui est efficace dans le traitement et la prévention de la sclérose en plaques. En outre, la présente invention concerne un procédé de traitement et de prévention de la sclérose en plaques utilisant le fait qu'un peptide comprenant une séquence du numéro d'identification de séquence selon la présente invention, un peptide comprenant une séquence présentant 80% d'homologie avec la séquence ci-dessus ou un fragment de peptide de celui-ci, présente d'excellents effets de traitement et de prévention de la sclérose en plaques. Plus spécifiquement, la présente invention concerne un procédé de traitement et de prévention de la sclérose en plaques sans effet secondaire par l'administration du peptide à un faible dosage.
PCT/KR2014/007545 2013-08-14 2014-08-13 Composition de traitement et de prévention de la sclérose en plaques Ceased WO2015023132A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7030211B1 (en) * 1998-07-08 2006-04-18 Gemvax As Antigenic peptides derived from telomerase
KR20120011883A (ko) * 2009-05-05 2012-02-08 모르포시스 아게 다발성 경화증의 치료
KR20120064981A (ko) * 2010-12-10 2012-06-20 한국과학기술연구원 다발성신경경화증의 치료 또는 예방용 조성물 및 이의 스크리닝 방법
KR20120103591A (ko) * 2009-10-12 2012-09-19 라이프바이오 라보라토리즈 엘엘씨 다발성 경화증 치료용 조성물
KR20130088783A (ko) * 2012-01-31 2013-08-08 주식회사 바이로메드 다발성 경화증의 예방 또는 치료용 조성물

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8828403B2 (en) * 2008-06-16 2014-09-09 Mediolanum Farmaceutici S.P.A. Anti-tumor immunotherapy
KR101713166B1 (ko) 2011-12-30 2017-03-07 박형진 말똥진흙버섯 추출물을 포함하는 다발성 경화증 및 자가면역성 질환의 예방 및 치료용 조성물

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7030211B1 (en) * 1998-07-08 2006-04-18 Gemvax As Antigenic peptides derived from telomerase
KR20120011883A (ko) * 2009-05-05 2012-02-08 모르포시스 아게 다발성 경화증의 치료
KR20120103591A (ko) * 2009-10-12 2012-09-19 라이프바이오 라보라토리즈 엘엘씨 다발성 경화증 치료용 조성물
KR20120064981A (ko) * 2010-12-10 2012-06-20 한국과학기술연구원 다발성신경경화증의 치료 또는 예방용 조성물 및 이의 스크리닝 방법
KR20130088783A (ko) * 2012-01-31 2013-08-08 주식회사 바이로메드 다발성 경화증의 예방 또는 치료용 조성물

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