2022 Fiscal Year Annual Research Report
Drug screening system for early pathology of SBMA using disease specific iPSCs and novel biomarkers
| Project/Area Number |
20K16587
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| Research Institution | Aichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | Motor Neurons / SBMA / Neurodegeneration / iPSC |
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| Outline of Annual Research Achievements |
Spinal and bulbar muscular atrophy (SBMA) is an adult-onset slowly progressive motor neuron (MN) disease caused by mutations in the Androgen Receptor (AR) affecting its normal functioning through pathways yet unknown. Current treatments for SBMA target only its symptoms, and animal models developed thus far have been lacking, creating a need for the development of more appropriate human models. Induced Pluripotent Stem Cells (iPSCs) have in recent years become a valuable tool for developing human models of several diseases, and our group has established SBMA disease specific iPSCs and generated an early-disease model using iPSC-derived MNs. Given that SBMA occurs at a later stage in life, recapitulating pathology using iPSC-derived MNs requires long-term culture and phenotypes are relatively mild, making further studies on the molecular causes of the disease difficult. In this project we have determined that optimizing culture conditions through the addition of stressors induces a marked early onset of pathology specifically in SBMA MNs, facilitating comparisons and allowing a clearer observation of phenotypes. Furthermore, this optimization allows us to better understand the molecular causes of the disease and helps open potential new
avenues for treatment of SBMA in the future.
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[Presentation] Elucidating early pathophysiology of spinal-bulbar muscular atrophy using disease-specific iPSCs2022
Author(s)
小野寺一成, 下門大祐, Bruno De Araujo Herculano, 石原康晴, 依田真由子, 太田明伸, 矢野真人, 宮冬樹, Rashid Muhammad Irfanur, 伊藤卓治, 岡田梨奈, 角田達彦, 細川好孝, 道勇学, 祖父江元, 勝野雅央,岡野栄之,岡田洋平
Organizer
第63回日本神経学会学術大会
