Elucidation of common neuromuscular pathomechanism in multisystem proteinopathy and search for therapeutic target molecules

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16571
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Tohoku University
• Principal Investigator: Izumi Rumiko 東北大学, 大学病院, 助教 (60571453)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 多系統蛋白質症 / 封入体 / トランスクリプトーム解析

Outline of Final Research Achievements

Comprehensive genomic analysis of pathologically diagnosed cases of inclusion body myopathy revealed hnRNPA1 gene mutations in 3 cases from 2 families, leading to the diagnosis of multisystem proteinopathy type 3 (MSP3). Furthermore, transcriptome analysis using MSP3 skeletal muscle specimen revealed that multiple pathways related to hnRNPA1 function were significantly suppressed in the MSP3 group. We evaluated the expression and localization of key molecules in these pathways using skeletal muscle tissue and patient-derived iPS cells, and examined their relationship with hnRNPA1 to verify their pathological significance. In addition, more than 300 molecules showed altered splice patterns in MSP3 skeletal muscle specimen, suggesting its involvement in muscle degeneration.

Free Research Field

脳神経内科

Academic Significance and Societal Importance of the Research Achievements

網羅的遺伝子解析により、多系統蛋白質症の新規診断例が加わった。そのことにより骨格筋組織を用いた病理学的解析・トランスクリプトーム解析が可能となり、本症における筋変性機序の一端を明らかとすることができた。さらに、共通する新たな治療標的分子を明らかにすることができれば、神経筋に共通する変性病態解明が大きく前進し、その成果は、筋萎縮性側索硬化症、前頭側頭型認知症、封入体形成筋疾患の治療法開発に広く応用できると期待される。