Establishment of Structure-Based Combination Therapy for Human Prion Disease

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16920
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: University of Miyazaki
• Principal Investigator: Takatsuki Hanae 宮崎大学, 医学部, 助教 (80773978)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: プリオン病 / 試験管内プリオン増幅法

Outline of Final Research Achievements

Prion disease is a neurodegenerative disorder caused by the accumulation of abnormal prion protein in the central nervous system. In this study, we examined the inhibitory effect of drugs on abnormal prion amplification using the in vitro prion amplification assay (PMCA assay).
Fifty-eight compounds were added to the PMCA reaction as candidate compounds for therapeutic agents, and their inhibitory effects were examined. Three compounds were found to suppress the amplification of the Fukuoka-1 strain, an acclimated strain of hereditary human prion disease. However, the scrapie acclimation strain, 22-L, showed different results from those of Fukuoka-1, indicating that the anti-prion effects of drugs differed among prion strains.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

プリオン病は異常型プリオンタンパク質が中枢神経系に蓄積することで発症する神経変性疾患である。本研究の成果は２つあり、1つはプリオン株ごとに阻害剤の抑制効果が異なることを明確に示したこと。もう一つはプリオン潜伏感染という現象を初めて発見したことである。今後このメカニズムを解明することで、予防薬の開発のための知見が得られるだけでなく、発症要因が不明であった孤発性クロイツフェルト・ヤコブ病の発症機構の解明につながる可能性が期待される。