| Project/Area Number |
26461268
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Nagoya University |
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Principal Investigator |
Sahashi Kentaro 名古屋大学, 医学部附属病院, 病院助教 (90710103)
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| Co-Investigator(Kenkyū-buntansha) |
祖父江 元 名古屋大学, 医学系研究科, 特任教授 (20148315)
勝野 雅央 名古屋大学, 医学系研究科, 教授 (50402566)
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| Co-Investigator(Renkei-kenkyūsha) |
OKADA Yohei 愛知医科大学, 医学部, 特任准教授 (30383714)
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| Research Collaborator |
Bennett C. Frank Ionis Pharmaceuticals, Senior Vice President
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 球脊髄性筋萎縮症 / 運動ニューロン疾患 / アンチセンス核酸 / 病態解明 / 変異アンドロゲン受容体 / RNA / 病態 / 分子標的治療 |
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| Outline of Final Research Achievements |
Spinal and bulbar muscular atrophy or SBMA results from mutations in the AR gene and elicits motor deficits due to lower motor neuron and muscle degeneration. Toxicity of abnormal AR protein causes SBMA, but the primary pathogenic region remains elusive. Antisense oligonucleotides (ASOs) can control gene expression and contribute to identification of the target for the development of therapeutics. Here we have found that an intracerebroventricular injection of ASOs suppressing AR expression in the central nervous system, improves motor function, weight gain and survival with the amelioration of neuronal histopathology in an SBMA mouse model, focusing the neurotoxicity of mutant AR as a therapeutic target. This study further supports the applicability of antisense therapeutics for SBMA.
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