| Project/Area Number |
19390240
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
URUSHITANI Makoto Shiga University of Medical Science, 分子神経科学研究センター, 准教授 (60332326)
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| Co-Investigator(Kenkyū-buntansha) |
高橋 良輔 京都大学, 医学研究科, 教授 (90216771)
舘野 美奈子 国立精神神経センター, 神経研究所, 室長 (50332325)
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| Co-Investigator(Renkei-kenkyūsha) |
TAKAHASHI Ryosuke 京都大学, 医学部, 教授 (90216771)
TATENO Minako 国立精神神経センター, 神経研究所, 室長 (50332325)
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2009: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2008: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2007: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
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| Keywords | 神経病態生化学 / 筋萎縮性側索硬化症 / ワクチン / 抗体療法 / 免疫療法 / ミクログリア / 運動ニューロン死 / ハイブリドーマ / superoxide dismutase 1(SOD1) / グリア細胞 |
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| Research Abstract |
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown etiology. The aim of this research project was to improve the vaccination and a passive immunization with a novel monoclonal antibody against mutant SOD1 using ALS model mice, and to clarify the roles of microglia in mutant SOD1-linked ALS. We found apo-form of WT SOD1 is an effective vaccine compared with mutant SOD1, which induces a protective immunity with the increase in interleukin-4 and the decrease in interferon-gamma and tumor necrosis alpha. The therapeutic effect of intrathecal infusion of one clone of the mutant SOD1-specific antibodies to slow the progression was confirmed. We also clarified the crucial role of CD14 of the microglia in extracellular SOD1 mutant-induced motor neuron death. Further development of immunotherapy for ALS can be anticipated by defining more crucial molecular target or manipulating monoclonal antibody.
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