| Project/Area Number |
17K09773
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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 | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 神経再生 / 運動ニューロン / アストロサイト / 神経炎症 / 神経変性 / 神経科学 / 再生医学 / 脳神経疾患 |
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| Outline of Final Research Achievements |
Amyotrophic lateral sclerosis (ALS) is an adult-onset, devastating neurodegenerative syndrome characterized by systemic loss of motor neurons with prominent gliogenesis in the central nervous system. We focused on bone morphogenetic proteins (BMP) as a major soluble protein that promotes astrocytogenesis and its activation in the adult spinal cord. In a transgenic rat model with ALS-linked mutant Cu/Zn superoxide dismutase gene, BMP-4 was progressively up-regulated in spinal ventral horn reactive astrocytes, whereas noggin, a BMP-antagonist, was decreased. Continuous intrathecal infusion of either noggin or Bmp4-targeted antisense oligonucleotides after disease onset significantly ameliorated motor dysfunction and neurogenic muscle atrophy, and also extended survival of ALS model rats, by reducing astrocytogenesis, astrocytic activation, and neuroinflammation. The BMP-4 and its downstream signaling may be a novel therapeutic target for disease-modifying therapies in ALS.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果は、成人発症の難治性・進行性疾患の代表である筋萎縮性側索硬化症（ALS）において骨形成蛋白質（BMP）とその下流シグナルが新たな進行抑制治療の標的となり得ることを初めて明らかにしたものである。ALS同様に神経炎症を伴う他の神経変性疾患への応用も期待され、人口の高齢化とともに増加しつつある神経変性疾患の新しい進行抑制療法の開発につながると期待される。
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