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WO2013047889A1 - Composition pharmaceutique pour le traitement de maladies auto-immunes - Google Patents

Composition pharmaceutique pour le traitement de maladies auto-immunes Download PDF

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Publication number
WO2013047889A1
WO2013047889A1 PCT/JP2012/075587 JP2012075587W WO2013047889A1 WO 2013047889 A1 WO2013047889 A1 WO 2013047889A1 JP 2012075587 W JP2012075587 W JP 2012075587W WO 2013047889 A1 WO2013047889 A1 WO 2013047889A1
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sirna
seq
expression
pharmaceutical composition
heavy chain
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Japanese (ja)
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康二 安友
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University of Tokushima NUC
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University of Tokushima NUC
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1138—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against receptors or cell surface proteins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]

Definitions

  • the present invention relates to a novel use of a functional nucleic acid related to CD98. More specifically, the present invention relates to a pharmaceutical composition for treating autoimmune disease using CD98 siRNA. More specifically, the present invention relates to a therapeutic agent for diabetes (particularly type 1 diabetes) and a pharmaceutical composition for treating rheumatoid arthritis.
  • CD98 is a heterodimeric glycoprotein of approximately 120 kDa that is widely expressed on the cell membrane and is thought to be associated with amino acid transport, increased cell membrane expression and cell fusion associated with integrin-mediated adhesion .
  • the structure of CD98 is heterozygous by disulfide bond with one of approximately 80 kDa type II transmembrane protein CD98hc (heavy chain: 4F2hc, SLC3A2) and one of six types of approximately 40 kDa light chain (LAT1, LAT2, y + LAT1, y + LAT2, xCT, asc). It constitutes a dimer and functions as an amino acid transporter.
  • CD98hc The heavy chain of CD98 (CD98hc) has a role of transferring a dimer to the cell membrane, and the light chain (lc) is considered to have a transporter function.
  • CD98hc was first discovered as a T cell activation antigen and is a glycoprotein having various functions. Its function is highly expressed in proliferating lymphocytes, tumor cells, and other highly proliferative cells, and plays an important role in integrin-dependent signals that promote tumorigenesis.
  • Amino acid transport system that CD98 is involved is composed from one to reflect the diversity of the amino acid molecules as substrates six transporters (the light chain of about 40 kDa), the transport substrate selectivity and Na + It is classified into various transport systems by dependence.
  • CD98 heavy chain is present in the cell membrane on the blood vessel side of the epithelial cells and functions to transport the transporter to the cell membrane on the blood vessel side of the epithelial cells.
  • CD98 is known to be highly expressed in various cancer cells. The reason for this is that cancer cells need to actively take in essential amino acids necessary for growth in order to promote cell growth, and it is considered that neutral amino acid transporters are overexpressed there.
  • L-type amino acid transporter 1 has been cloned as an amino acid transporter that is highly expressed specifically in cancer cells (Kanai et al., J. Biol. Chem. (1998), 273). , 23629-23632).
  • LAT1 forms a complex with CD98 heavy chain and has a function of transporting neutral amino acids having large side chains such as leucine, valine, phenylalanine, tyrosine, tryptophan, methionine, and histidine independent of sodium ions. ing.
  • This LAT1 is low in expression or not observed in most normal tissues except brain, placenta, bone marrow, and testis, but colon cancer, stomach cancer, breast cancer, pancreatic cancer, renal cancer, laryngeal cancer, esophagus
  • CD98 CD98 heavy chain and light chain
  • LAT1 suppressing amino acid uptake
  • Patent Documents 2 and 3 In addition, in order to suppress amino acid transport of CD98 (a complex of heavy chain and light chain), an inhibitory effect on cancer cells using an anti-CD98 antibody has been reported in a cancer transplanted mouse model (Patent Documents 2 and 3). As described above, various attempts have been made to use anti-CD98 antibodies as anticancer agents. However, there are almost no efforts for applications other than anticancer drugs. Moreover, no attempt has been made to try to evaluate the therapeutic effect of the anticancer agent and the like by suppressing the expression of CD98 using siRNA.
  • the object of the present invention is to provide a pharmaceutical composition for autoimmune diseases using a functional nucleic acid of CD98.
  • an object of the present invention is to provide a pharmaceutical composition containing siRNA that suppresses CD98 heavy chain expression as an active ingredient.
  • the present inventor has identified a monoclonal antibody that recognizes the heavy chain of CD98, and found that this monoclonal antibody suppresses activation of T cells.
  • the present inventors have found that this antibody does not affect amino acid transport and suppresses cell adhesion via fibronectin. Then, when this antibody was used to treat diabetic NOD mice, it was possible to suppress the activation of CD4 + T cells and return the diabetic state to the normal level (PCT / JP2011 / 057432). Therefore, the present inventor treated diabetic NOD mice using siRNA that suppresses the expression of CD98 heavy chain.
  • the siRNA against CD98 heavy chain not only suppressed the progression of type 1 diabetes, but also the treatment. I found out that I can do it.
  • siRNA capable of suppressing the expression of CD98 heavy chain was administered to rheumatoid arthritis model mice, it was confirmed that the onset of arthritis was suppressed.
  • a pharmaceutical composition containing siRNA of CD98 as an active ingredient is effective for treatment / prevention of autoimmune diseases (type 1 diabetes, rheumatoid arthritis, etc.). From these findings, it was shown that the siRNA of the present invention is useful as a therapeutic agent for autoimmune diseases.
  • a pharmaceutical composition for preventing or treating an autoimmune disease comprising a functional nucleic acid that suppresses the expression of CD98 heavy chain as an active ingredient.
  • the functional nucleic acid is siRNA.
  • the autoimmune disease is type 1 diabetes or rheumatoid arthritis.
  • the siRNA is a double-stranded RNA.
  • the above (4) description, wherein the double-stranded RNA is an siRNA containing one or more of SEQ ID NO: 1 and SEQ ID NO: 2, SEQ ID NO: 3 and SEQ ID NO: 4, or SEQ ID NO: 5 and SEQ ID NO: 6.
  • the double-stranded RNA is an siRNA containing one or more of SEQ ID NO: 7 and SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO: 10, or SEQ ID NO: 11 and SEQ ID NO: 12.
  • Pharmaceutical composition (7) Double-stranded siRNA having any one of SEQ ID NO: 1 and SEQ ID NO: 2, SEQ ID NO: 3 and SEQ ID NO: 4, or SEQ ID NO: 5 and SEQ ID NO: 6.
  • Double-stranded siRNA in which the double-stranded RNA portion has any one of SEQ ID NO: 7 and SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO: 10, or SEQ ID NO: 11 and SEQ ID NO: 12.
  • a method for treating an autoimmune disease comprising administering to a mammal an effective amount of a functional nucleic acid that suppresses the expression of CD98 heavy chain.
  • the functional nucleic acid is siRNA.
  • the siRNA is the double-stranded siRNA of (7) or (8).
  • the autoimmune disease is type 1 diabetes or rheumatoid arthritis.
  • the pharmaceutical composition and the therapeutic method of the present invention are useful for the treatment of autoimmune diseases. Very useful. It is particularly effective for type 1 diabetes and rheumatoid arthritis, for which there has been no effective treatment.
  • FIG. 1 T cells of NOD mice that have developed type 1 diabetes are administered to NOD model mice (NOD-SCID mice) with severe combined immunodeficiency. After administration, mice are administered mouse siRNA against CD98 heavy chain (4 nmol / mouse) or control siRNA on days 2, 5, and 8. The day on which T cells are administered is taken as the starting date.
  • FIG. 1 is a diagram in which the expression of CD98 heavy chain in peripheral blood mononuclear cells after 3 days was evaluated by flow cytometry.
  • the gray (GRAY) part is the measurement result when the CD98 antibody was administered.
  • the dotted line portion shows the measurement results when the control siRNA is administered, and the solid line portion shows the measurement results when the siRNA against CD98 heavy chain is administered.
  • FIG. 1 is a diagram in which the expression of CD98 heavy chain in peripheral blood mononuclear cells after 3 days was evaluated by flow cytometry.
  • the gray (GRAY) part is the measurement result when the CD98 antibody was administered.
  • the dotted line portion shows the measurement
  • FIG. 2 is a diagram showing blood glucose levels measured and evaluated in order to see the therapeutic effect of type 1 diabetes. The experiment was conducted with 5 mice as a group, and the symbol * indicates a statistically significant difference (p ⁇ 0.05).
  • a dotted line part is a result at the time of administering control siRNA, and a continuous line part is a result at the time of administering siRNA with respect to CD98 heavy chain.
  • FIG. 3 shows the results of intraperitoneal administration of siRNA on day 0, day 1, day 2, day 3, day 4 using rheumatoid model mice (collagen-induced arthritis model). . The result shows that the onset of rheumatism is greatly reduced by administration of mouse siRNA.
  • FIG. 1 shows that the onset of rheumatism is greatly reduced by administration of mouse siRNA.
  • FIG. 4 is a diagram in which human siRNA was administered to Jurkat cells derived from human T lymphoma, and changes in the expression of CD98 protein on the cell surface were measured and evaluated using a flow cytometer. Compared with the untreated group and the control siRNA administration group, the suppression of the expression of CD98 protein was greatly suppressed by administering human siRNA.
  • a pharmaceutical composition for preventing or treating an autoimmune disease comprising a functional nucleic acid that suppresses the expression of CD98 heavy chain as an active ingredient
  • CD98 heavy chain a method for treating an autoimmune disease, which comprises administering an effective amount of a functional nucleic acid that suppresses the expression of an ".
  • CD98 is a known protein, and the DNA sequence and amino acid sequence are described in Patent Document 2 and the like.
  • CD98 in the present invention is not limited to these sequences, and the number of amino acid and DNA mutations and mutation sites are not limited as long as the function of CD98 is maintained.
  • “functional nucleic acid” refers to siRNA, miRNA, aptamer, ribozyme, and antisense nucleic acid having a function capable of suppressing protein expression.
  • Preferred examples include siRNA. That is, the siRNA of the present invention refers to an siRNA that suppresses gene expression of CD98 heavy chain. Specifically, it refers to siRNA that can suppress the gene expression of CD98 by 50% or more, and preferably siRNA that can suppress 80% or more compared to the control group (when control siRNA is used). siRNA is known to induce sequence-specific suppression of gene expression called RNA interference.
  • siRNA is generally composed of a double-stranded RNA portion and an overhang portion at the 3 ′ end of the sense strand and the antisense strand.
  • siRNAs can be designed by methods known to those skilled in the art. For example, a selected DNA sequence (preferably 19 to 21 bases) is directly converted into an RNA sequence (sense strand) and its antisense strand as a double-stranded RNA portion, and an overhang portion is added.
  • the overhang portion is an arbitrary nucleic acid (ribonucleic acid or deoxynucleic acid) having 1 or 2 bases, and uridine (U) or thymidine (dT) is preferable.
  • the siRNA of the present invention is not particularly limited as long as it is designed based on the DNA sequence of CD98, preferably human CD98 heavy chain, and can suppress the expression of CD98 heavy chain.
  • the suppression of expression is desirably specific for the CD98 heavy chain. Whether it is specific or not can be confirmed by conducting a publicly available BLAST search.
  • the overhang part is not essential.
  • the siRNA of the present invention also includes any molecule having the same effect as the siRNA of the present invention within the administration subject.
  • An example of such a molecule is shRNA.
  • shRNA is RNA having a short hairpin structure, and is an RNA molecule having a stem-loop structure so that a part of a single strand forms a complementary strand with another region.
  • ShRNA in which the double-stranded RNA portion has the same structure as the siRNA of the present invention is also included in the siRNA of the present invention.
  • a DNA that can express the siRNA of the present invention by being administered to an administration subject is also included in the siRNA of the present invention.
  • Such a DNA is used by constructing a DNA encoding siRNA into an expression vector (for example, a vector such as adenovirus, adeno-associated virus, herpes virus, lentivirus).
  • an expression vector for example, a vector such as adenovirus, adeno-associated virus, herpes virus, lentivirus.
  • a functional nucleic acid when used as a pharmaceutical composition, it is desirable to include a modification for improving the properties as a therapeutic agent or a transport carrier such as a liposome.
  • nucleotide modifications or analogs can be introduced. For example, improved nuclease resistance and / or improved cell permeability. Nuclease resistance is brought about by any method known in the art that does not interfere with the biological activity of the antisense, siRNA, shRNA and / or ribozyme.
  • An example of a modification that can be added to an oligonucleotide for the purpose of improving nuclease resistance is modification of a heteroatom's phosphorus or oxygen in the phosphate backbone. For example, methyl phosphate, phosphorothioate, phosphorodithioate, and morpholino oligomers.
  • the functional nucleic acid when used as a pharmaceutical composition or a treatment method in the present invention, there are a method of using the functional nucleic acid itself for treatment and a method of expressing the functional nucleic acid using a vector and using it for the treatment. To do.
  • the functional nucleic acid itself is used for treatment, it is desirable to prepare an aqueous solution to which a stabilizer such as atelocollagen, a pH regulator and the like are added and administered parenterally as it is.
  • an expression vector particularly a mammalian expression vector, particularly for expression in a patient requiring the treatment of the present invention.
  • Expression vectors are well known in the art and preferably include plasmids, cosmids, and viral expression systems. Examples of preferred virus expression systems are adenovirus, retrovirus, lentivirus and the like.
  • methods for introducing vectors into cells and tissues are well known in the art. Preferred examples include transfection, lipofection, electroporation, and infection with recombinant viral vectors.
  • the “mammal” of the present invention include rodents such as rats, mice, and guinea pigs, such as dogs and cats, and humans and monkeys.
  • the “autoimmune disease” of the present invention is a disease caused by the immune system raising autoantibodies against endogenous antigens.
  • type 1 diabetes rheumatoid arthritis, ulcerative colitis, psoriasis, Crohn's disease, systemic lupus erythematosus And Graves' disease.
  • Previous studies have revealed that any autoimmune disease is caused by abnormal overactivation of T cells.
  • CD4 positive or CD8 positive T lymphocytes (T cells) are excessively activated to promote the production of autoantibodies or cause tissue destruction, which has a great influence on the progress of disease states. It is a fact that.
  • the siRNA of the present invention suppresses the activation of T lymphocytes (T cells) similarly to the anti-CD98 antibody, the above-described autoimmune diseases can be treated using the siRNA of the present invention.
  • the siRNA of the present invention is effective for the treatment of type 1 diabetes, and as shown in FIG. 3, it is effective for the treatment of rheumatoid arthritis.
  • the siRNA of the present invention can be used for the treatment of autoimmune diseases such as type 1 diabetes, rheumatoid arthritis, ulcerative colitis, psoriasis, Crohn's disease, systemic lupus erythematosus, and Graves' disease.
  • preferred uses of the siRNA of the present invention are type 1 diabetes, rheumatoid arthritis, ulcerative colitis, psoriasis, Crohn's disease, systemic lupus erythematosus, and Graves' disease, and particularly preferred uses include type 1 diabetes or Rheumatoid arthritis can be mentioned.
  • “Rheumatoid arthritis” of the present invention refers to an autoimmune disease in which joints, bones, muscles, ligaments, tendons, etc. hurt, and the most frequent autoimmune disease, which is often difficult to treat following a very chronic course It is.
  • the siRNA of the present invention having an action of suppressing activation of T cells (T lymphocytes) is suitable for the treatment of rheumatoid arthritis.
  • the “type 1 diabetes” of the present invention refers to a disease in which pancreatic ⁇ -cells are destroyed mainly by autoimmunity and insulin production is depleted, resulting in insulin deficiency.
  • the siRNA of the present invention having an activity of suppressing activation of T cells (T lymphocytes) is suitable for the prevention and treatment of type 1 diabetes.
  • the pharmaceutical composition is used together with the above-described functional nucleic acid and one or more kinds of conventional pharmaceutically acceptable additives. Is preferably prepared and administered.
  • the pharmaceutical composition of the present invention is preferably administered parenterally, and can be administered intravenously, intramuscularly, intraperitoneally, or subcutaneously.
  • the dose of the functional nucleic acid of the present invention varies depending on the administration subject, administration method, and the like. For example, when administered parenterally, for example, about 0.01 to about 1 day per day for an autoimmune disease patient (60 kg). 30 mg, preferably about 0.1 to 20 mg, more preferably about 0.1 to 10 mg can be intravenously injected.
  • Experimental Materials a) Animals: Type 1 diabetes model mouse (NOD mouse): NOD-SCID mice were purchased from Japan SLC (Hamamatsu, Japan). All mice were kept under aseptic conditions in the Tokushima University Animal Center, and all experiments were conducted according to animal management and utilization guidelines. The development of diabetes in NOD mice was monitored by measuring the urine sugar concentration and fasting blood glucose level of each mouse every week.
  • a mouse having a blood concentration of 250 mg / dl or more was considered diabetic. When female mice with NOD reach 20-25 weeks of age, they have type 1 diabetes at a rate of 80% or more.
  • a fluorescent dye-conjugated antibody eBioscience, UAS
  • TCRV ⁇ 2 TCRV ⁇ 5
  • Mouse siRNA A mixture of the three mouse siRNAs shown in Table 1 below for suppressing the expression of CD98 heavy chain, or a control siRNA having no target gene (B-Bridge) was used. 2) Method: A mixture of the above three siRNAs for suppressing the expression of CD98 heavy chain, or a control siRNA having no target gene and atelocollagen (Koken, Japan) were mixed according to the experimental procedure to prepare a siRNA solution.
  • the siRNA solution was intraperitoneally administered at 4 nmol / mouse to a severe combined immunodeficiency model mouse (NOD-SCID mouse) to which T cells of diabetic NOD mice were administered.
  • the administration schedule of siRNA is the 2nd day, the 5th day, and the 8th day. The day on which the T cells are administered is taken as the starting date.
  • Three days after administration of the siRNA solution blood was collected, white blood cells were isolated, stained with anti-mouse CD98 antibody, and evaluated by flow cytometry. 3) Results: The evaluation results by flow cytometry are shown in FIG.
  • the gray (GRAY) part is the measurement result when the CD98 antibody was administered.
  • FIG. 2 shows the results of administering CD98 heavy chain siRNA to the type 1 diabetes model mouse (NOD-SCID mouse). As shown in FIG. 2, it was found that the progression of type 1 diabetes in this mouse can be suppressed by administration of siRNA. This result indicates that CD98 plays a crucial role in the development of type 1 diabetes and that treatment with siRNA targeting the CD98 heavy chain is self-induced due to type 1 diabetes and other T cells.
  • Example 2 Rheumatoid arthritis progression inhibition test with siRNA for suppressing expression of CD98 heavy chain
  • Experimental materials Production of rheumatoid model mice (collagen-induced arthritis model mice): DBA / 1J mice (7-week-old female, 10 mice) were divided into two groups, respectively, and administered with an emulsion in which bovine collagen II and complete adjuvant were mixed and emulsified. Furthermore, the second bovine collagen II was administered on the 26th day, and the onset of arthritis was observed and evaluated. In FIG. 3, the clinical score is expressed as the mean ⁇ standard deviation. The horizontal axis represents the number of days after the second collagen immunization.
  • CD98 plays a very important role in the development of type 1 diabetes, and treatment using siRNA targeting the CD98 heavy chain is very useful for the prevention and treatment of autoimmune diseases (rheumatic). Is effective.
  • Example 3 CD98 expression progression suppression test of human leukemia T cells (Jurkat cells) by siRNA for suppressing expression of CD98 heavy chain 1)
  • Experimental materials Jurkat cells: Jurkat cells that highly express human CD98 protein were purchased from ATCC.
  • a siRNA was prepared from a mixture of the three human siRNAs shown in Table 2 below for suppression of CD98 heavy chain expression (requested from B-Bridge) and used.
  • 3) Results The ratio of CD98 expression on the Jurkat cell surface was measured and evaluated with a flow cytometer, and the results are shown in FIG. As shown in FIG. 4, in the control siRNA administration group, the protein expression of CD98 was the same as that in the non-treatment group. However, in the group administered with human siRNA, protein expression of CD98 was suppressed by about 75%. This indicates that these three types of human siRNA can be used to prevent and treat type 1 diabetes and other autoimmune diseases caused by T cells.
  • the pharmaceutical composition for prevention and treatment of autoimmune diseases of the present invention prevents and treats autoimmune diseases (for example, in type 1 diabetes and rheumatoid arthritis) by a new mechanism of action that suppresses the expression of CD98 by siRNA. To get.
  • autoimmune diseases for example, in type 1 diabetes and rheumatoid arthritis
  • siRNA siRNA

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Abstract

La présente invention concerne une composition pharmaceutique et une méthode de traitement à la fois pour traiter/prévenir des maladies auto-immunes. Il s'avère qu'une composition pharmaceutique contenant un ARNsi qui peut inhiber l'expression d'une chaîne lourde de CD98 est utile pour la prévention/le traitement de maladies auto-immunes. Par conséquent, il devient possible de fournir une nouvelle méthode de traitement à l'aide de l'ARNsi pour des maladies auto-immunes, telles que le diabète de type 1 et une polyarthrite rhumatoïde.
PCT/JP2012/075587 2011-09-27 2012-09-26 Composition pharmaceutique pour le traitement de maladies auto-immunes Ceased WO2013047889A1 (fr)

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Citations (2)

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JP2010540595A (ja) * 2007-10-04 2010-12-24 フエー・イー・ベー・フエー・ゼツト・ウエー アルツハイマー病に対する細胞外標的
WO2012026526A1 (fr) * 2010-08-27 2012-03-01 国立大学法人宮崎大学 Récepteur d'hémokinine 1 et peptide dérivé d'hémokinine 1

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Title
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