Elucidation of early pathology of motor neuron diseases using disease specific iPSCs

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H03576
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Aichi Medical University
• Principal Investigator: Okada Yohei 愛知医科大学, 加齢医科学研究所, 教授 (30383714)
• Co-Investigator(Kenkyū-buntansha): 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 – 2022-03-31
• Keywords: 疾患iPS細胞 / 運動ニューロン疾患 / 早期病態

Outline of Final Research Achievements

Spinal bulbar muscular atrophy (SBMA) is an adult-onset motor neuron degenerative disease. Previous analysis has shown the pathogenesis induced by mutant androgen receptor (AR) aggregates, however, recent analysis suggested pathology independent of mutant AR aggregates. Moreover, leuprorelin treatment has shown to be effective especially in patients in the early stage of the disease. In this study, we generated an early disease model using motor neurons derived from SBMA disease-specific iPSCs, and identified molecules that were involved in the early pathology of SBMA. Inhibitors of the identified molecules and their downstream molecules rescued the phenotype, suggesting that these molecules could be novel therapeutic targets of SBMA.

Free Research Field

神経内科学　幹細胞生物学　分子神経生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、SBMA疾患特異的iPS細胞を用いることで、SBMAの早期病態を再現し得る病態モデルを作成し、早期病態に関与する分子を同定することができた。また、これらの分子の病態への関与を解析することで、SBMAの早期病態の一部を解明し、新規治療標的を同定することができた。今後は、同定した分子を足がかりにSBMAの早期病態の詳細を解明するとともに、新規治療開発に向けた解析を進めていく予定である。