| Project/Area Number |
20K16587
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 52020:Neurology-related
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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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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | Motor Neurons / SBMA / Neurodegeneration / iPSC / Motor neurons |
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| Outline of Research at the Start |
Spinal and bulbar muscular atrophy (SBMA) is an adult onset, slowly progressive motor neuron disease characterized whose causes are not completely understood and for which there is no effective treatment. We aim to use motor neurons generated from SBMA patient-derived induced pluripotent stem cells (iPSCs) to develop an objective and efficient system to evaluate pathological changes in these neurons with the goal of better understanding the causes of the disease. We also aim to utilize this system to screen known compounds with the potential to prevent the onset or progression of SBMA.
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| Outline of Final Research Achievements |
Spinal and bulbar muscular atrophy (SBMA) is an adult-onset slowly progressive motor neuron (MN) disease caused by the expansion of CAG repeat in the Androgen Receptor (AR) gene, for which current treatments are ineffective. Induced Pluripotent Stem Cells (iPSCs) are a valuable tool for developing reproducible models of diseases, and we succeeded in developing a model of SBMA using iPSC-derived MNs. In this project we developed an optimized culture system incorporating stressors that facilitates the observation of the SBMA in cultured MNs, clarified the molecular mechanisms contributing to disease onset and progression and developed appropriate isogenic control cell lines, facilitating comparisons and allowing a clearer observation of phenotypes. These results allow us to more clearly investigate the etiology of SBMA and test novel potentially life-saving treatments.
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| Academic Significance and Societal Importance of the Research Achievements |
Currently there is no effective treatment for SBMA. Our research has perfected an iPSC model of SBMA and clarified molecular mechanisms causing the disease, allowing for faster screening of potential drugs for its treatment, and better understanding of the intracellular causes of the disease.
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