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Treatment of myocardial infarction by a novel drug to reduce endoplasmic reticulum stress

Research Project

Project/Area Number 18K15888
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53020:Cardiology-related
Research InstitutionDepartment of Clinical Research, National Hospital Organization Kyoto Medical Center (2020)
Kyoto University (2018-2019)

Principal Investigator

Ide Yuya  独立行政法人国立病院機構(京都医療センター臨床研究センター), 展開医療研究部, 研究員 (20804206)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords心筋梗塞 / 新規化合物 / 心保護作用 / ATP / 小胞体ストレス / 虚血再灌流 / 心保護効果 / 虚血再灌流障害 / 再灌流後投与
Outline of Final Research Achievements

We evaluated cardio-protective effects of KUS121 (Kyoto University Substance 121). KUS121 protected H9C2 rat cardiomyoblasts from cell death by reducing ER stress, and preserving ATP levels. In murine myocardial infarction models, KUS121 treatment was able to reduce the myocardial infarct size by administration after reperfusion. This improvement was also associated with reductions in ER stress and the maintenance of ATP levels. We examined whether KUS121 could produce therapeutic effects in porcine myocardial infarction models. Intracoronary administration of KUS121 attenuated the infarcted area in a dose-dependent manner. The efficacy of KUS121 as a promising novel therapeutic agent for myocardial infarction.

Academic Significance and Societal Importance of the Research Achievements

急性心筋梗塞に対する治療法は、カテーテル治療(経皮的冠動脈インターベンション)が第一選択の治療法である。しかし、それでも心筋梗塞を完全には改善させるには至らない。しかしながら、心筋梗塞サイズをさらに減らすための新たな手技や治療薬は未だ確立されたものはないというのが現状である。KUS121の投与によってマウス心筋梗塞モデルの梗塞サイズを減少させただけではなく、ブタの心筋梗塞モデルを用いた実際の治療を見据えた投与方法によっても梗塞サイズを減少させることを実証した。KUS121は急性心筋梗塞に対する新たな治療法となる可能性があり、心筋梗塞による死亡率を低下させ、心不全を減少させることも期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2020 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] Cardioprotective Effects of VCP?Modulator KUS121 in Murine and Porcine Models of Myocardial Infarction2019

    • Author(s)
      Ide Yuya, at al.
    • Journal Title

      JACC: Basic to Translational Science

      Volume: 4 Issue: 6 Pages: 701-714

    • DOI

      10.1016/j.jacbts.2019.06.001

    • NAID

      120006734885

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Myocardial Infarction-Our current study investigating a new treatment for MI2020

    • Author(s)
      Yuya Ide
    • Organizer
      第84回日本循環器学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Cardioprotective Effects of VCP Modulator KUS121 in Animal Models of Myocardial2020

    • Author(s)
      Yuya Ide
    • Organizer
      第84回日本循環器学会学術集会
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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