Protein anchoring therapy for disorders of signal transmission at the neuromuscular junction

• Project/Area Number: 19700364
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurophysiology and muscle physiology
• Research Institution: Nagoya University
• Principal Investigator: MIKAKO Ito Nagoya University, 大学院・医学系研究科, 助教 (60444402)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: 分子欠損症 / 神経筋接合部 / collagen Q / AChE欠損症 / 先天性筋無力症候群 / 遺伝子治療 / 細胞外分子欠損症

Research Abstract

神経筋接合部のcollagen Q (ColQ)欠損による終板アセチルコリンエステラーゼ(AChE)欠損症に対するタンパク係留療法の開発を行った。アデノ随伴ウィルスベクターを介してCOLQ遺伝子をColqノックアウトマウスに導入したところ、顕著な運動機能の回復が見られ、神経筋接合部にColQが集積しAChE活性があることが確認できた。ColQは神経筋接合部に集積する細胞外分子であるため、自らの係留シグナルにより生体内の筋組織に伝達・補充され、治療効果が高く現れたと考えられる。

Research Products

• [Journal Article] Molecular bases and therapeutic strategies in defective neuromuscular transmissions: lessons learned from a prototypical synapse. (2009)
  • Author(s): Ohno K, Ito M, Masuda A.
  • Journal Title: 日本神経精神薬学雑誌 29(4)(review) Pages: 145-51
  • NAID: 10025185971
• [Journal Article] Molecular bases and therapeutic strategies in defective neuromuscular transmissions : lessons learned from a prototypical synapse. (review) (2009)
  • Author(s): Ohno K, Ito M, Masuda A.
  • Journal Title: 日本神経精神薬学雑誌 4 Pages: 145-151
• [Journal Article] Viral vector-mediated expression of human collagen Q in cultured cells. (2008)
  • Author(s): Ito M, Masuda A, Jinno S, Katagiri T, Krejci E, Ohno K.
  • Journal Title: Chem Biol Interact 175 Pages: 346-348
  • Peer Reviewed
• [Journal Article] Viral vector-medicated expression of human collage Q in cultured cells (2008)
  • Author(s): Mikako Ito, Akio Masuda, Shinsuke Jinno, Takeshi Katagiri, Eric Krejci, Kinji Ohno^a
  • Journal Title: CHEMICO-BIOLOGICAL INTERACTIONS (in press)
  • Peer Reviewed
• [Presentation] rAAV8-Mediated Protein Anchoring of Asymmetric Acetylcholinesterase (Ache)to the Synaptic Basal Lamina at the Neuromuscular Junction (NMJ). (2008)
  • Author(s): Ito M, Suzuki Y, Okada T, Fukudome T, Yoshimura T, Masuda A, Takeda S, Krejci E, Ohno K
  • Organizer: 48th Annual Meeting. The American Society for Cell Biology
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2008-12-16
• [Presentation] Adeno-associated virus serotype 8-mediated targeting of asymmetric acetylcholinesterase to the synaptic basal lamina at the neuromuscular junction. (2008)
  • Author(s): Ito M, Suzuki Y, Okada T, Fukudome T, Masuda A, Yoshimura T, Takeda S, Krejci E, Ohno K
  • Organizer: 38th Annual Meeting, Society for Neuroscience
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2008-11-19
• [Presentation] rAAV8-mediated protein anchoring therapy for congenital defect of collagen Q. (2008)
  • Author(s): Ito M, Suzuki Y, Okada T, Takeda S, Fukudome T, Yoshimura T, Krejci E, Ohno K
  • Organizer: 第14回日本遺伝子治療学会総会
  • Place of Presentation: 札幌医科大学
  • Year and Date: 2008-06-13
• [Presentation] Gene therapy for collagen Q defects in congenital myasthenic syndromes (2007)
  • Author(s): M. Ito, A. Masuda, S. Jinno, T. Katagiri, E. Krejci and K. Ohno
  • Organizer: The IXth International Meeting on Cholinesterases
  • Place of Presentation: 中国、蘇州
  • Year and Date: 2007-05-07