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Development of a novel treatment for SMA using SMA-iPSCs disease models with different genetic background

Research Project

Project/Area Number 16K10008
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research Institution独立行政法人国立病院機構長良医療センター(臨床研究部)

Principal Investigator

FUNATO Michinori  独立行政法人国立病院機構長良医療センター(臨床研究部), 長良医療センター臨床研究部, 第二小児科医長 (30420350)

Research Collaborator OHUCHI Kazuki  
ANDO Shiori  
SATO Arisu  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords疾患モデル / iPS細胞 / 薬剤応答性 / 治療薬開発 / 創薬 / 薬剤反応性 / 神経科学 / 再生医学
Outline of Final Research Achievements

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by the degeneration of spinal motor neurons. This disease is caused by the deletion of the survival motor neuron protein. Currently, there are no curative agents for SMA, although some research groups have developed treatments based on the molecular pathophysiology of this disease. Our purpose in this study is to establish a number of human SMA with different genetic background-derived induced pluripotent stem cells (SMA-iPSCs) disease model and develop a standard treatment for SMA.
Before now, we established SMA-iPSCs disease models derived from 19 SMA patients with different genetic background. In addition, we assayed a therapeutic drug of thyrotropin-releasing hormone (TRH) analog, a free radical scavenger (edaravone), a docosahexaenoic acid, γ-secretase inhibitor, and rufinamide.

Academic Significance and Societal Importance of the Research Achievements

SMAは難治性の希少疾患ではあるが、背景にひそむ病態は多種多様である。本研究によって、薬剤の応答性の個人差が解明されれば、希少疾患におけるテーラーメイド医療へのさらなる道筋を提示することになる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (10 results)

All 2019 2018 2017 2016

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (5 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Impairment of oligodendrocyte lineages in Spinal Muscular Atrophy Model Systems2019

    • Author(s)
      Ohuchi K, Funato M, Ando S, Inagaki S, Sato A, Kawase C, Seki J, Nakamura S, Shimazawa M, Kaneko H and Hara H
    • Journal Title

      NeuroReport

      Volume: 30(5) Issue: 5 Pages: 350-357

    • DOI

      10.1097/wnr.0000000000001206

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Notch Signaling Mediates Astrocyte Abnormality in Spinal Muscular Atrophy Model Systems2019

    • Author(s)
      Ohuchi Kazuki、Funato Michinori、Yoshino Yuta、Ando Shiori、Inagaki Satoshi、Sato Arisu、Kawase Chizuru、Seki Junko、Saito Toshio、Nishio Hisahide、Nakamura Shinsuke、Shimazawa Masamitsu、Kaneko Hideo、Hara Hideaki
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 3710-3710

    • DOI

      10.1038/s41598-019-39788-w

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Protective Effects of Levetiracetam on a Human iPSCs-Derived Spinal Muscular Atrophy Model.2019

    • Author(s)
      Ando S, Funato M, Ohuchi K, Inagaki S, Sato A, Seki J, Kawase C, Saito T, Nishio H, Nakamura S, Shimazawa M, Kaneko H, Hara H.
    • Journal Title

      Neurochem Res.

      Volume: in press Issue: 7 Pages: 1773-1779

    • DOI

      10.1007/s11064-019-02814-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A docosahexaenoic acid-derived pro-resolving agent, maresin 1, protects motor neuron cells death2018

    • Author(s)
      Ohuchi K., Ono Y., Joho M., Tsuruma K., Ogami S., Yamane S., Funato M., Kaneko H., Nakamura S., Hara H. and Shimazawa M
    • Journal Title

      Neurochemical Research

      Volume: 43(7) Issue: 7 Pages: 1413-1423

    • DOI

      10.1007/s11064-018-2556-1

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Edaravone is a candidate agent for spinal muscular atrophy: In vitro analysis using a human induced pluripotent stem cells-derived disease model.2017

    • Author(s)
      Ando S, Funato M, Ohuchi K, Kameyama T, Inagaki S, Seki J, Kawase C, Tsuruma K, Shimazawa M, Kaneko H, Hara H.
    • Journal Title

      Eur J Pharmacol.

      Volume: 814 Pages: 161-168

    • DOI

      10.1016/j.ejphar.2017.08.005

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The protective effects of levetiracetam on spinal muscular atrophy models.2018

    • Author(s)
      Ando S., Ohuchi K., Funato M., Nakamura S., Shimazawa M., Kaneko H. and Hara H.
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Skeletal muscle atrophy and impaired myogenesis in spinal muscular atrophy.2018

    • Author(s)
      Ando S., Ohuchi K., Funato M., Nakamura S., Shimazawa M., Kaneko H. and Hara H.
    • Organizer
      1st Global Congress of Pharmacy Faculties
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The neuroprotective effects of edaravone in generated spinal motor neuron using iPSCs derived from a spinal muscular atrophy patient2017

    • Author(s)
      Shiori Ando, Michinori Funato, Kazuki Ohuchi, , Kazuhiro Tsuruma, Masamitsu Shimazawa, Hideo Kaneko, and Hideaki Hara
    • Organizer
      the 14th Asian and Oceanian Congress of Child Neurology (AOCCN2017)
    • Place of Presentation
      Fukuoka
    • Year and Date
      2017-05-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] The Protective Effects of Edaravone in Generated Spinal Motor Neuron Using iPSCs Derived from a Spinal Muscular Atrophy Patient2017

    • Author(s)
      Ando S., Funato M., Ohuchi K., Tsuruma K., Shimazawa M., Kaneko H. and Hara H.
    • Organizer
      14th Asian and Oceanian Congress of Child Neurology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脊髄性筋萎縮症病態におけるグリア系譜細胞の分化異常の関与2016

    • Author(s)
      大内一輝、舩戸道徳、川瀬千鶴、関順子、安藤栞、稲垣賢、鶴間一寛、嶋澤雅光、金子英雄、原英彰
    • Organizer
      第130回日本薬理学会近畿部会
    • Place of Presentation
      京都
    • Year and Date
      2016-11-19
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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