Examination of treatment of myasthenia gravis with antibodies against muscle-specific kinase using experimental animal model.

• Project/Area Number: 23791009
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: MORI Shuuichi 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (30508677)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 神経分子病態学 / 神経筋シナプス / 重症筋無力症 / MuSK

Research Abstract

This study examined the availability of a novel drug in the treatment of myasthenia gravis with antibodies against muscle-specific kinase (MuSK-MG) using experimental animal model. The results provided the evidence that only low-dose cholinesterase inhibitors should be used to avoid side effect, and that 3,4-diaminopyridine will be effective as a mainstay in the symptomatic therapy of MuSK-MG.

Research Products

• [Journal Article] Mechanisms associated with the pathogenicity of antibodies against muscle-specific kinase in myasthenia gravis. (2013)
  • Author(s): Mori S, Shigemoto K.
  • Journal Title: Autoimmun Rev Volume: (in press) Issue: 9 Pages: 912-7
  • DOI: 10.1016/j.autrev.2013.03.005
  • Peer Reviewed
• [Journal Article] 神経筋接合部の異常と筋萎縮 (2013)
  • Author(s): 森 秀一, 重本 和宏
  • Journal Title: 医学のあゆみ Volume: 244 Pages: 696-703
• [Journal Article] サルコペニア発症のメカニズム (2013)
  • Author(s): 宮崎剛
  • Journal Title: 腎と骨代謝 Volume: 26 Pages: 99-107
• [Journal Article] 神経筋接合部の維持機構と筋萎縮 (2013)
  • Author(s): 森秀一
  • Journal Title: 医学のあゆみ Volume: 244 Pages: 696-703
• [Journal Article] 筋肉と神経－最新知見を踏まえて (2013)
  • Author(s): 重本和宏
  • Journal Title: Bone Joint Nerve Volume: 3 Pages: 27-31
• [Journal Article] 筋肉の老化 (2013)
  • Author(s): 重本和宏
  • Journal Title: Clinical Calcium Volume: 23 Pages: 23-28
• [Journal Article] Intracellular and extracellular ATP coordinately regulate the inverse correlation between osteoclast survival and bone resorption. (2012)
  • Author(s): Miyazaki T, Iwasawa M
  • Journal Title: J Biol Chem. Volume: 287(45) Issue: 45 Pages: 34808-23
  • DOI: 10.1074/jbc.m112.385369
  • Peer Reviewed
• [Journal Article] (2012)
  • Author(s): 森 秀一, 山田 茂, 秋好 沢諭, 福永 大地, 重本 和宏
  • Journal Title: 健康医科学 Volume: 27 Pages: 148-56
• [Journal Article] 3,4-Diaminopyridine improves neuromuscular transmission in a MuSK antibody-induced mouse model of myasthenia gravis (2012)
  • Author(s): Mori, S. , Kishi, M., Kubo, S., Akiyoshi, T., Yamada, S., Miyazaki, T., Konishi, T., Maruyama, N., and Shigemoto, K.
  • Journal Title: Journal of neuroimmunology Volume: 245 Issue: 1-2 Pages: 75-78
  • DOI: 10.1016/j.jneuroim.2012.02.010
  • Peer Reviewed
• [Journal Article] Divalent and monovalent autoantibodies cause dysfunction of MuSK by distinct mechanisms in a rabbit model of myasthenia gravis (2012)
  • Author(s): Mori, S. , Yamada, S., Kubo, S. , Chen, J., Matsuda, S. , Shudou, M. , Maruyama, N., and Shigemoto, K.
  • Journal Title: Journal of neuroimmunology Volume: 244 Issue: 1-2 Pages: 1-7
  • DOI: 10.1016/j.jneuroim.2011.12.005
  • Peer Reviewed
• [Journal Article] Antibodies against muscle-specific kinase impair both presynaptic and postsynaptic functions in a murine model of myasthenia gravis (2012)
  • Author(s): Mori S, Kubo S, Akiyoshi T, Yamada S, Miyazaki T, Hotta H, Desaki J, Kishi M, Konishi T, Nishino Y, Miyazawa A, Maruyama N, Shigemoto K
  • Journal Title: The American Journal of Pathology Volume: 180 Issue: 2 Pages: 617-28
  • DOI: 10.1016/j.ajpath.2011.10.031
  • Peer Reviewed
• [Journal Article] 老齢マウスの筋線維タイプ特異的な筋萎縮の病態解明 (2012)
  • Author(s): 福永大地
  • Journal Title: 基礎老化研究 Volume: 36 (3) Pages: 47-49
• [Journal Article] Ezetimibe decreases SREBP-1c expression in liver and reverses hepatic insulin resistance in mice fed a high-fat diet (2011)
  • Author(s): Muraoka T, Aoki K, Iwasaki T, Shinoda K, Nakamura A, Aburatani H, Mori S, Tokuyama K, Kubota N, Kadowaki T, Terauchi Y
  • Journal Title: Metabolism Volume: 60 Issue: 5 Pages: 617-28
  • DOI: 10.1016/j.metabol.2010.06.008
  • NAID: 40018948824
  • Peer Reviewed
• [Journal Article] Establishment and characterization of hepatocytes from an Immortomouse/SMP30/GNL knockout mouse hybrid lacking vitamin C to study vitamin C transport (2011)
  • Author(s): Amano, A., Handa, S., Aigaki, T., Shigemoto, K., Maruyama, N., Ishigami, A.
  • Journal Title: Journal of biochemistry Volume: 150 Issue: 6 Pages: 671-678
  • DOI: 10.1093/jb/mvr109
  • Peer Reviewed
• [Presentation] 3,4-diaminopyridine to treatment of a MuSK antibody-induced mouse model of myasthenia gravis. (2012)
  • Author(s): Mori S.
  • Organizer: 日本神経科学学会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-09-21
• [Presentation] 神経筋シナプスの維持メカニズムの解明とサルコペニア研究への展開 (2012)
  • Author(s): 森 秀一
  • Organizer: 日本体力医学会
  • Place of Presentation: 岐阜
  • Year and Date: 2012-09-15
• [Presentation] 抗MuSK抗体陽性重症筋無力症の発症メカニズムに基づく治療薬の検討 (2012)
  • Author(s): 森 秀一.
  • Organizer: 日本神経学会
  • Place of Presentation: 東京
  • Year and Date: 2012-05-25
• [Presentation] Distinct mechanism between divalent and monovalent MuSK antibodies are involved with dysfunction of MuSK leading to myasthenia gravis. (2011)
  • Author(s): Mori S.
  • Organizer: Society of Neuroscience
  • Place of Presentation: Washington, D.C. (USA)
  • Year and Date: 2011-11-15
• [Presentation] MuSK とDok-7の相互作用は神経筋シナプスの維持に重要である (2011)
  • Author(s): 森 秀一
  • Organizer: 日本体力医学会
  • Place of Presentation: 下関
  • Year and Date: 2011-09-17
• [Presentation] Distinct mechanism between divalent and monovalent MuSK antibodies are involved with dysfunction of MuSK leading to myasthenia gravis. (2011)
  • Author(s): Mori S.
  • Organizer: 日本神経科学学会
  • Place of Presentation: 横浜
  • Year and Date: 2011-09-15
• [Presentation] Distinct mechanisms between divalent and monovalent MuSK antibodies involved with dysfunction of MuSK leading to myasthenia gravis. (2011)
  • Author(s): Mori S
  • Organizer: 第34回日本神経科学会大会
  • Place of Presentation: 横浜
• [Presentation] MuSKとDok-7の相互作用は神経筋シナプスの維持に重要である. (2011)
  • Author(s): 森秀一
  • Organizer: 第66回日本体力医学会大会
  • Place of Presentation: 下関
• [Presentation] Distinct mechanisms between divalent and monovalent MuSK antibodies involved with dysfunction of MuSK leading to myasthenia gravis. (2011)
  • Author(s): Mori S
  • Organizer: Society for Neuroscience
  • Place of Presentation: Washington DC
• [Presentation] Effectiveness of 3,4-diaminopyridine to treatment of a MuSK antibody-induced mouse model of myasthenia gravis.
  • Author(s): Mori S
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] 神経筋シナプスの維持メカニズムの解明とサルコペニア研究への展開
  • Author(s): 森秀一
  • Organizer: 第67回日本体力医学会大会
  • Place of Presentation: 岐阜
• [Presentation] 抗MuSK抗体陽性重症筋無力症の発症メカニズムに基づく治療薬の検討
  • Author(s): 森秀一
  • Organizer: 第53回日本神経学会学術大会
  • Place of Presentation: 東京
• [Book] 運動神経細胞とサルコペニア (2011)
  • Author(s): 重本和宏
  • Total Pages: 2
  • Publisher: 新興医学出版社
• [Remarks]
  • URL: http://www.tmghig.jp/J_TMIG/j_research/DA33.html