Elucidaion of muscular pathology of SBMA using disease specific iPSCs

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K07969
• 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: Aichi Medical University
• Principal Investigator: Doyu Manabu 愛知医科大学, 医学部, 教授 (90293703)
• Co-Investigator(Kenkyū-buntansha): 岡田 洋平 愛知医科大学, 加齢医科学研究所, 教授 (30383714) ; 伊藤 卓治 愛知医科大学, 加齢医科学研究所, 助教 (30794151)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 疾患iPS細胞 / 球脊髄性筋萎縮症 / 骨格筋

Outline of Final Research Achievements

Spinal bulbar muscular atrophy (SBMA) is a slowly progressive lower motor neuron degenerative disease that occurs in males in their 30s to 50s. Although motor neuron degeneration has been considered the main pathogenesis of SBMA, skeletal muscle itself or skeletal muscle-induced neurodegeneration has been suggested, and elucidation of skeletal muscle pathology has been expected. In this study, we developed a culture method to rapidly and efficiently induce the differentiation of human iPSCs into skeletal muscle, and differentiated SBMA disease-specific iPSCs into skeletal muscle for pathological analysis. As a result, it was found that skeletal muscle derived from SBMA patients exhibited pathological conditions such as increased expression of genes involved in muscle differentiation and decreased expression of fast-twitch muscle markers, suggesting the involvement of the muscle pathology in SBMA.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

SBMAでは、これまで運動ニューロンに着目した病態解析が数多く進められてきたが、近年では骨格筋病態の重要性が示唆されている。また、モデルマウスとヒト患者では骨格筋病理がやや異なることなどから、よりヒト患者の病態を忠実に反映する疾患モデルが求められてきた。本研究では、ヒトiPS細胞から迅速・高効率に骨格筋を分化誘導する培養法を確立し、患者由来骨格筋における病態を明らかにすることができた。今後の病態解明、創薬研究に有用な知見が得られたと考えられる。