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2023 Fiscal Year Final Research Report

Construction of a next-generation human prion amplification method and its application to drug screening for human prion diseases

Research Project

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Project/Area Number 21K07277
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionUniversity of Miyazaki

Principal Investigator

Takatsuki Hanae  宮崎大学, 医学部, 助教 (80773978)

Co-Investigator(Kenkyū-buntansha) 中垣 岳大  長崎大学, 医歯薬学総合研究科(医学系), 准教授 (80722917)
Project Period (FY) 2021-04-01 – 2024-03-31
Keywordsプリオン病 / 試験管内プリオン増幅法
Outline of Final Research Achievements

Two in vitro prion amplification methods were used to screening for prion disease therapeutics. As a result, we found a compound that inhibited the Fukuoka-1 strain. However, this compound was suggested to produce drug-resistant prions by in vitro prion amplification. When the therapeutic effect of this compound on mice infected with the Fukuoka-1 prion strain was examined, survival of the treated mice was not significantly different from that of the non-treated group. On the other hand, survival of mice treated with the compound from 90 days after infection was prolonged. Detecting drug resistance before conducting animal studies is a key to improving the efficiency of therapeutic drug development. In the future, we will examine whether in vitro prion amplification can be a tool to predict the emergence of drug-resistant prions.

Free Research Field

神経変性疾患

Academic Significance and Societal Importance of the Research Achievements

クロイツフェルト・ヤコブ病に代表されるプリオン病は致死性神経変性疾患であり治療法はない。これまでに治療薬として期待された化合物にはプリオン感染細胞で抑制効果が示されたものの、感染マウスにおける耐性プリオンの出現により有効性が制限された事例もある。長期に及ぶ動物試験を行う前に薬剤耐性プリオンの出現を見抜くことは治療薬開発の効率化の鍵となる。本研究で見出された治療薬候補化合物は動物試験において薬剤耐性プリオンが出現したことが示唆され、試験管内プリオン増幅法においても耐性プリオンが出現することが確認された。今後、試験管内プリオン増幅法が薬剤耐性プリオンの出現を予測するツールに成り得るか検討する。

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Published: 2025-01-30  

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