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

2012 Fiscal Year Final Research Report

• 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
• 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)
  • DOI: 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] Intracellular and extracellular ATP coordinately regulate the inverse correlation between osteoclast survival and bone resorption. (2012)
  • Author(s): Miyazaki T, Iwasawa M, Nakashima T, Mori S, Shigemoto K, Nakamura H, Katagiri H, Takayanagi S, Tanaka S.
  • Journal Title: J Biol Chem Volume: 287 Pages: 37808-23
  • DOI: 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] Maruyama N, Shigemoto K. 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, Shigemoto K.
  • Journal Title: J Neuroimmunol Volume: 245 Pages: 75-8
  • DOI: DOI:10.1016/j.jneuroim.2012.02.010
  • Peer Reviewed
• [Journal Article] Divalent and monovalent autoantibodies cause dysfunction of MuSK by distinct mechanism in a rabbit model of myasthenia gravis. (2012)
  • Author(s): ori S, Yamada S, Kubo S, Chen J, Matsuda S, Shudou M, Maruyama N, Shigemoto K.
  • Journal Title: J Neuroimmunol Volume: 244 Pages: 1-7
  • DOI: 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: Am J Pathol Volume: 180 Pages: 798-810
  • DOI: DOI:10.1016/j.ajpath.2011.10.031
  • Peer Reviewed
• [Journal Article] Ezetimide 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 Pages: 617-28
  • DOI: DOI:10.1016/j.metabol.2010.06.008
  • 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