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Therapeutic trials for progressive muscular dystrophy by using mdx mice

Research Project

Project/Area Number 03670426
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionToho University School of Medicine

Principal Investigator

KURIHARA Teruyuki  M.D.Toho Univ.Professor, 医学部, 教授 (80098607)

Co-Investigator(Kenkyū-buntansha) KISHI Masahiko  M, D, Toho Univ. Assistant, 医学部, 助手 (50204847)
Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1992: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1991: ¥700,000 (Direct Cost: ¥700,000)
KeywordsMdx Mouse / Bestation / Mexiletine / Diphenylhydantoin / Dantrolene Na / Drug Effect / Resting Membrane Potential / Electrical Myotonia / 筋ジストロフィー / 薬物治療 / マウス / 電気的ミオトニ-
Research Abstract

Duchenne's muscular dystrophy and X chromosome-linked mouse mutant (mdx) have been found to have the same defect of dystrophin in the muscle surface membrane. Intracellular recordings from the mdx mouse hemidiaphragm preparations revealed a group of muscle fibers with low resting membrane potentials (RMP) and electrical myotonia in about 30 % of the impaled muscle fibers at low temperature below 26゚C. The purpose of this study is to find effective medications to improve these physiological abnormalities of mdx mice.
In 1991 we have studied the effect of bestatin, mexyletine, and diphenylhydantoin on mdx mouse hemidiaphragm preparations. The intracellular recordings revealed that both bestatin and mexyletine improved low RMP, but diphenylhydantoin did not imprvove low RMP. All the above three medications suppressed electrical myotonia of mdx mice.
Bertorini reported that dantrolene Na reduced serum CK levels and suppressed the progression of muscle weakness in Duchenne's muscular dystrophy in 1991. Therefore, we also applied this medication to mdx mice in 1992. Dantorolene Na was given to mdx mice intraperitoneally for two weeks with a dose of 10 mg/day. We also studied the in vitro effect of dantrolene Na on mdx mouse hemidiaphragm preparations with a concentration of 10mg/1 in Tyrode's solution. The results showed that dantrolene Na did not improve low RMP of mdx mice, nor suppressed electrical myotonia.
In conclusion only bestation and mexiletine improved low RMP of mdx mice and suppressed electrical myotonia among the four medications we have tested for possible therapeutic usage.

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] 栗原 照幸: "進行性筋ジストロフィー症治療の展望" 神経治療学. 10. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 栗原 照幸ほか: "最新医学からのアプローチ「イオンチャネル」9-4)筋緊張症" メジカルビュー社, (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 栗原 照幸: "myotoniaの病態生理,栗原照幸ら編「モダンコンセプト神経内科4」" 医学書院, (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kurihara T: "Therapeutic trials and prospects for progressive muscular dystrophy" Neurological Therapeutics. 10(3). (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 栗原 照幸: "進行性筋ジストロフィー症治療の展望" 神経治療学. 10. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 栗原 照幸 ほか: "最新医学からのアプローチ「イオンチャネル」 9-4)筋緊張症" メジカルビュー社, (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 栗原 照幸ほか: "mdxマウスの電気的病態と薬物治療,筋活動電位の分析,及びミオトニ-の数理的解析" 厚生省「精神・神経疾患研究委託費」筋ジストロフィ-及び関連疾患の成因と治療開発に関する研究。荒木班平成3年度報告書. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 日高 隆信: "mdxマウスの横隔膜標本における電気生理学的変化およびMexiletine,Diphenylhydantoinにより効果" 東邦医会誌. 38. 544-551 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 栗原 照幸: "myotoniaの病態生理,栗原照幸ら編「モダンコンセプト神経内科IV」" 医学書院, (1993)

    • Related Report
      1991 Annual Research Report
  • [Publications] 栗原 照幸: "先天性筋緊張症パラミオトニア,亀山 正邦,高倉 公朋編「今日の神経疾患治療指針」" 医学書院, (1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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