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development of a new remedy for muscular dystrophies

Research Project

Project/Area Number 15K08312
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionSapporo Medical University

Principal Investigator

Horio Yoshiyuki  札幌医科大学, 医学部, 教授 (30181530)

Co-Investigator(Kenkyū-buntansha) 浜田 博喜  岡山理科大学, 理学部, 教授 (10164914)
Co-Investigator(Renkei-kenkyūsha) NIKAIDO Koki  札幌医科大学, 医学部, 小児科学講座 (90359993)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsSIRT1 / レスベラトロール / 筋ジストロフィー / オートファジー / マイトファジー / 活性酸素 / 臨床研究 / ミトコンドリア / ROS / Duchenne型 / Becker型 / 福山型
Outline of Final Research Achievements

There exists few remedy to muscular dystrophies (MD) except glucocorticoids, but there is no report of glucocorticoids for extending walking ability more than 2 years. We found that resveratrol, an activator of SIRT1, is effective on dystrophin-deficient mdx mice.
In the present study, we found that autophagy of damaged mitochondria containing deleted mitochondria DNA was suppressed in mdx mice. Damaged mitochondria liberate high levels of reactive oxygen species (ROS). Resveratrol reactivated the autophagy, which cleared damaged mitochondria and reduced ROS. Administration of resveratrol to 11 MD patients for 24 weeks showed resveratrol was effective on MD. Resveratrol significantly increased motor function and enhanced muscle strength with quantitative muscle testing. Thus, resveratrol will be a promising remedy for MD.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (17 results)

All 2017 2016 2015 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (9 results) (of which Invited: 2 results) Remarks (1 results)

  • [Journal Article] 筋ジストロフィーの新治療法の開発2017

    • Author(s)
      久野篤史、細田隆介、堀尾嘉幸
    • Journal Title

      メディカル・サイエンス・ダイジェスト

      Volume: 42 Pages: 38-42

    • Related Report
      2017 Annual Research Report
  • [Journal Article] SIRT1: A Novel Target for the Treatment of Muscular Dystrophies.2016

    • Author(s)
      Kuno A, Horio Y.
    • Journal Title

      Oxid Med Cell Longev.

      Volume: 未定 Issue: 1 Pages: 6714686-6714686

    • DOI

      10.1155/2016/6714686

    • Related Report
      2017 Annual Research Report 2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Biochemical effects of the flavanol-rich lychee fruit extract on the melanin biosynthesis and reactive oxygen species.2016

    • Author(s)
      Hagiwara K, Okura M, Sumikawa Y, Hida T, Kuno A, Horio Y, Yamashita T.
    • Journal Title

      J Dermatol.

      Volume: 未定 Issue: 10 Pages: 1174-1183

    • DOI

      10.1111/1346-8138.13326

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 筋ジストロフィーの新治療法の開発2016

    • Author(s)
      久野篤史、細田隆介、堀尾嘉幸
    • Journal Title

      Medical Science Digest

      Volume: 42 Pages: 642-646

    • Related Report
      2016 Research-status Report
  • [Journal Article] 長寿遺伝子サーチュイン2016

    • Author(s)
      堀尾嘉幸、國本梨沙、久野篤史
    • Journal Title

      THE LUNG perspectives

      Volume: 24 Pages: 303-306

    • Related Report
      2016 Research-status Report
  • [Journal Article] The effects of resveratrol and SIRT1 activation on dystrophic cardiomyopathy.2015

    • Author(s)
      Kuno A, Tanno M, Horio Y.
    • Journal Title

      Ann N Y Acad Sci.

      Volume: 1348 Issue: 1 Pages: 46-54

    • DOI

      10.1111/nyas.12812

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Sirt1-deficient mice have hypogonadotropic hypogonadism due to defective GnRH neuronal migration.2015

    • Author(s)
      Di Sante G, Wang L, Wang C, Jiao X, Casimiro MC, Chen K, Pestell TG, Yaman I, Di Rocco A, Sun X, Horio Y, Powell MJ, He X, McBurney MW, Pestell RG.
    • Journal Title

      Mol Endocrinol

      Volume: 29 Issue: 1 Pages: 200-212

    • DOI

      10.1007/s11060-014-1686-9

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] SIRT1はドキソルビシン誘導性心筋障害を悪化させる2017

    • Author(s)
      細田隆介、久野篤史、塚本美樹、堀尾嘉幸
    • Organizer
      日本薬理学会
    • Place of Presentation
      長崎新聞文化ホール(長崎県長崎市)
    • Year and Date
      2017-03-15
    • Related Report
      2016 Research-status Report
  • [Presentation] タンパク質脱アセチル化酵素SIRT1の分子機能とその筋ジストロフィーへの応用2017

    • Author(s)
      堀尾嘉幸
    • Organizer
      第69回北日本小児科学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Role of impaired autophagy caused by aberrant activation of mTORC1 in dystrophic cardiomyopathy.2017

    • Author(s)
      Kuno A, Hosoda R, Horio Y
    • Organizer
      Keystone Symposia Conference: Aging and Mechanisms of Aging-Related Disease
    • Related Report
      2017 Annual Research Report
  • [Presentation] Restoration of impaired autophagosome clearance underlies amelioration of cardiomyopathy afforded by SIRT1 activation in dystrophin-deficient mice.2017

    • Author(s)
      Kuno A, Hosoda R, Horio Y.
    • Organizer
      Cardiovascular and Metabolic Week 2017 (CVMW2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] レスベラトロールによる筋ジストロフィー改善におけるミトコンドリアオートファジーの役割2017

    • Author(s)
      瀬堀 理生、久野 篤史、細田 隆介、堀尾 嘉幸
    • Organizer
      第68回日本薬理学会北部会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 筋ジストロフィー心筋におけるオートファジー不全の意義2017

    • Author(s)
      久野 篤史、細田 隆介、瀬堀 理生、堀尾 嘉幸
    • Organizer
      第68回日本薬理学会北部会
    • Related Report
      2017 Annual Research Report
  • [Presentation] SIRT1は筋機能維持と筋障害軽減に働く2017

    • Author(s)
      瀬堀 理生、久野 篤史、細田 隆介、堀尾 嘉幸
    • Organizer
      第42回 日本分子生物学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 筋ジストロフィーに対するレスベラトロールの探索的臨床研究2015

    • Author(s)
      堀尾嘉幸、川村健太郎、福村忍、二階堂弘輝、舘延忠、畠山欣也、久原真、下濱俊、小塚直樹、林貴士、久野篤史、堤裕幸
    • Organizer
      第66回薬理学会北部会
    • Place of Presentation
      富山国際会議場(富山県富山市)
    • Year and Date
      2015-09-18
    • Related Report
      2015 Research-status Report
  • [Presentation] SIRT1の筋保護作用とその応用2015

    • Author(s)
      堀尾嘉幸、久野篤史、林貴士、國本梨沙、細田隆介、瀬堀理生、塚本美樹、川村健太郎、福村忍、二階堂弘輝、舘延忠、畠山欣也、久原真、下濱俊、小塚直樹、堤裕幸
    • Organizer
      第17回薬物活性シンポジウム
    • Place of Presentation
      新潟大学医学部有壬記念館
    • Year and Date
      2015-09-04
    • Related Report
      2015 Research-status Report
    • Invited
  • [Remarks] http://web.sapmed.ac.jp/pharmacology/index.html

    • Related Report
      2016 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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