Establishment of iPS cells from spinal and bulbar muscular atrophy and the research of polyglutamine diseases

Research Project

Project/Area Number	25860722
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Neurology
Research Institution	Keio University
Principal Investigator	Nihei Yoshihiro 慶應義塾大学, 医学部, 助教 (60468501)
Project Period (FY)	2013-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000) Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	ポリグルタミン病 / 球脊髄性筋萎縮症 / 神経変性疾患 / 運動ニューロン疾患 / アンドロゲン受容体 / 17-AAG / iPS細胞 / 筋萎縮性側索硬化症 / パーキンソン病 / トリプレットリピート病 / 凝集体 / dihydroteststerone
Outline of Final Research Achievements	We established spinal and bulbar muscular atrophy (SBMA)-derived iPS cells (iPSCs) and confirmed motor neuron differentiation. Aggregation of androgen receptor in SBMA-iPSC-derived neurons is enhanced by dihydrotestosterone. And one of the candidate drugs, 17-AAG promoted to degrade AR aggregation. These findings show iPSCs technology makes us be able to recapitulate disease-specific biochemical features and demonstrate the potential for identification and validation of candidate drugs. We also established iPSCs from other polyglutamine diseases (Machado-Joseph disease, Dentatorubral-pallidoluysian atrophy) and neurodegenerative diseases (amyotrophic lateral sclerosis, Parkinson's disease). We are going to advance the polyglutamine disease researches by using the established iPSC lines.