Development of curative therapy for polyglutamine disease by CAG repeat genome engineering

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K19465
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Neuroscience and related fields
• 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)
• Project Period (FY): 2017-06-30 – 2023-03-31
• Keywords: ゲノム編集 / 神経変性疾患 / ポリグルタミン病 / 根治的治療法

Outline of Final Research Achievements

With the recent advances in genome editing technology, the development of novel therapeutics for hereditary neurodegenerative diseases is expected. In this study, we targeted Spinal Bulbar Muscular Atrophy (SBMA), which is caused by abnormal expansion of the polyglutamine tract (CAG repeat) of the androgen receptor (AR) gene, and developed genome editing technology to control the CAG repeat length of the AR. As a result, we succeeded in expanding the normal CAG repeats of wild-type ARs in cultured cell lines to reproduce the phenotype, and in shortening the abnormal CAG repeats of mutant ARs to normal length in SBMA disease-specific iPSCs. This technology may be applicable to the development of curative therapies for various hereditary neurodegenerative diseases.

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

多くの遺伝子性神経変性疾患では、リピート配列の伸長により発症することが知られており、リピート配列の制御が根治的治療法の開発につながると考えられる。本研究の成果により、リピート配列の制御が可能になれば、様々な神経変性疾患の根治的治療法の開発につながると考えられる。