Multidimensional Analyses of the Central Nervous System Pathophysiology of Repeat Expansion Disease: Focusing on Myotonic Dystrophy

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07992
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Osaka University
• Principal Investigator: Takahashi Masanori 大阪大学, 医学系研究科, 教授 (20359847)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 筋強直性ジストロフィ / RNA / スプライシング / 中枢神経 / 認知機能

Outline of Final Research Achievements

The ultimate goal of this study was to elucidate the mechanisms of region-selectivity, which remain a crucial issue in the study of neurodegenerative diseases. Myotonic dystrophy (DM) was chosen as the primary focus of the study, as the understanding of its pathogenesis as an RNA disease is very advanced. We performed a comprehensive RNAseq analysis of each brain region using autopsied brains. We identified many splice abnormalities, including those previously reported, in the temporal lobe. Cerebellar-specific abnormalities were also identified. Inter-regional similarities were revealed between frontal and temporal lobes. RNAseq analysis was also performed on the liver to compare the differences between organs. We accumulated neuropsychological and MRI data and clarified the clinical characteristics of DM patients.

Free Research Field

脳神経内科

Academic Significance and Societal Importance of the Research Achievements

リピート病のひとつである筋強直性ジストロフィーを対象として、中枢神経におけるRNA異常の病態を網羅的解析により明らかにした。この成果は、他のリピート病や変性疾患での解析に役立つ基礎的データとなることが期待される。また、明らかにされた画像や神経心理学的特徴は、患者の臨床評価、治験におけるアウトカムメジャーとしても役立つと考えられる。