2023 Fiscal Year Final Research Report
Drug development of central nervous system disease using drug re-positioning
| Project/Area Number |
20K09351
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56010:Neurosurgery-related
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| Research Institution | Nagasaki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中川 慎介 福岡大学, 薬学部, 准教授 (10404211)
佐藤 慧 長崎大学, 医歯薬学総合研究科(医学系), 研究協力員 (40849486)
松永 裕希 長崎大学, 病院(医学系), 医員 (80772136)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | 血液脳関門 / 脳卒中 / Rho kinase阻害薬 / 中枢神経疾患治療薬 / ドラッグリポジショニング / in vitroモデル |
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| Outline of Final Research Achievements |
In the course of this research, we discovered and reported: 1) the characteristics of a co-culture model consisting of primary cultured cells of primates (monkeys), 2) the involvement of MAP kinase pathways in cerebral microvascular endothelial cells in the disruption of the blood-brain barrier by contrast agents, 3) the antagonistic effect of pitavastatin, a drug for treating dyslipidemia, on the disruption of the blood-brain barrier by inflammatory stimuli, and 4) the effect of Rho kinase inhibitors in protecting the blood-brain barrier. In drug repositioning, we also found that the blood-brain barrier protective function of Rho kinase inhibitors is effective in cerebral ischemia. This indicates the possibility of introducing this method in the field of cerebral infarction treatment in the future.
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| Free Research Field |
血液脳関門、脳卒中、脳神経外科
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| Academic Significance and Societal Importance of the Research Achievements |
脳梗塞治療は近年、血栓溶解療法に加え、カテーテルを用いた血栓回収療法が登場し、その治療成績は飛躍的に向上した。しかし、その時間的制約から、血栓回収療法を施行された患者の約半数は満足な回復が得られていない。我々が本研究で見出したRho kinase阻害薬のもつ血液脳関門保護機能および脳虚血に拮抗する作用を考慮すると、今後、血栓回収療法にRho kinase阻害薬動注療法を追加することで、脳梗塞患者の満足がいく回復につながる可能性がある。
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