2018 Fiscal Year Final Research Report
Elucidation of the pathogenesis of idiosyncratic drug-induced liver injury using HLA-transfected mice for establishment of preclinical prediction method
| Project/Area Number |
15H04661
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Chiba University |
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Principal Investigator |
Ito Kousei 千葉大学, 大学院薬学研究院, 教授 (30323405)
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| Co-Investigator(Kenkyū-buntansha) |
青木 重樹 千葉大学, 大学院薬学研究院, 助教 (30728366)
関根 秀一 千葉大学, 大学院薬学研究院, 講師 (70401007)
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| Research Collaborator |
Susukida Takeshi
Song Binbin
Fujimori Sota
Kogo Kotaro
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Keywords | 特異体質毒性 / 副作用個人差 / HLA / 薬物過敏症 |
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| Outline of Final Research Achievements |
Among the idiosyncratic toxicity, liver injury and skin hypersensitivity are considered to be complicated by multiple factors, and the elucidation of the mechanism has been delayed. In this study, we focused on drug hypersensitivity related to HLA polymorphism, which is considered to be difficult to reproduce in animals, and created the mouse model that can reproduce it for the first time. It has been confirmed that administration of certain drugs to this mouse causes organ damage via immune activation as seen in humans.
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| Free Research Field |
薬物毒性学
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| Academic Significance and Societal Importance of the Research Achievements |
発症に個人差の大きい特異体質性毒性は、製薬企業、患者の双方にとって厄介な問題で、現時点では医薬品開発途中でそのようなリスクを持つ化合物を見いだすことは困難である。特異体質毒性の発症メカニズム自体が不明であることがその原因の一つであった。本研究によって構築されたHLA多型導入マウスの利用により特異体質毒性の発症メカニズムの解明が飛躍的に進むと期待され、より安全な医薬品開発が行えるようになる点で社会的な意義がある。
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