| Project/Area Number |
18K15469
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 52020:Neurology-related
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
Hoshino Takao 東京女子医科大学, 医学部, 助教 (30724679)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2021: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 脳梗塞 / 脂質 / 炎症 / 脳保護療法 / PPARα / ペマフィブラート / PPARa / 脂質異常症 / 脳虚血 |
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| Outline of Final Research Achievements |
In mice middle cerebral artery occlusion models, pemafibrate significantly reduced the infarct volume and ameliorated functional outcomes. We also found that pemafibrate could reduce the levels of NF-kB, P-p38MAPK, and IL-1b in mice brain tissue, although the reproducibility was questionable. Antiinflammatory effects via PPARα activation in acute brain ischemia await further studies. In clinical studies, pemafibrate significantly reduced serum triglycerides and remnant-like particle cholesterol levels and increased HDL-cholesterol. In addition, significant reductions in ALT, γ-GTP, and IL-6 levels were also observed. To our knowledge, this study was the first report to show the antiinflammatory effects of pemafibrate in a clinical setting. We have published these data in J Atheroscler Thromb 2021.
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| Academic Significance and Societal Importance of the Research Achievements |
基礎研究では、ペマフィブラートによる急性期脳梗塞の改善効果を示すデータが得られ、その一端が抗炎症効果によるものである可能性が示唆された。現状では脳梗塞に対する脳保護療法や抗炎症治療の有効性は確立していないが、本薬剤が有望な治療となる可能性が示され、今後更なる検討を進める予定である。また臨床研究においては、ペマフィブラート投与により脂質プロファイルが著明に改善したとともに、炎症マーカーの低下も示された。本薬剤が脳梗塞後の残存リスクをさらに低減する新たな予防治療となることに期待が持てる結果であった。
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