| Project/Area Number |
13557056
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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 | 展開研究 |
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| Research Field |
Neurology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
KAJI Ryuji The University of Tokushima Hospital, Professor, 医学部附属病院, 教授 (00214304)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAMOTO Takashi The University of Tokushima, Hospital, Assistant, 医学部附属病院, 助手 (20343303)
IZUMI Yuishin The University of Tokushima, Hospital, Assistant, 医学部附属病院, 助手 (10335812)
NISHIMURA Masataka The University of Tokushima, Hospital, Lecturer, 医学部附属病院, 講師 (60335809)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Keywords | amyotrophic lateral sclerosis / methylcobalamin / vitamin B12 / SOD1-transgenic rat / therapy / animal model / fasciculation / SOD1 トランスジェニックマウス / 筋萎縮性訴句作硬化症 |
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| Research Abstract |
To develop a method of treating amyotrophic lateral sclerosis (ALS), a typical neurodegenerative disease of unknown etiology, we studied the effect of ultra-high dose methylcobalamin (>1mg/kg/day, I.m.) on clinical symptoms in patients with ALS and survival in an animal model. Ultra-high dose methylcobalamin is known to protect neurons from glutamate-induced excitatory cell death. The study of an animal model using wobbler mouse demonstrated a significantly longer survival of those treated with ultra-high dose methylcobalamin. That of SOD1-transgenic rat is still under way, with a promise of beneficial effects. After having an approval of the institutional review board of the ethics committee of Tokushima University and after obtaining informed consent, we compared the clinical signs and survivals between patients with ALS treated with regimen and those without it. In a long-term follow-up of patients, we demonstrated that this regimen significantly prolonged survivals in ALS. No major adverse effects were noted, and the safety was confirmed to be high. Thus this method may prove useful in larger clinical trials, and may give a therapeutic method for ALS. As a result of the present study, a clinical trial is going to be launched in Europe, starting this year. We also reviewed the pathophysiology of ALS using transcranial magnetic stimulation over the motor cortex, while the subject was minimally contracting the muscle to be tested. The timing of the motor unit discharge was analyzed using a post-stimulus time histograms (PSTHs), and a surge of the firing probability at 20-30 msec after the stimulation corresponds to the EPSP. In patients with early stage of ALS, this surge was significantly enhanced as compared to the normals. This is consistent with neuroexcitatory cell death, and also supports the efficacy of this regimen if given in the early stage of ALS.
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