权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

A Study of the Clinical Efficacy of Ultra-high Dose Methylcobalamin in Amyotrophic Lateral Sclerosis

超高剂量甲钴胺治疗肌萎缩侧索硬化症的临床疗效研究

基本信息

批准号：
13557056
负责人：
KAJI Ryuji
金额：
$ 2.11万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

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.

为了开发一种治疗肌萎缩侧索硬化症 (ALS)（一种病因不明的典型神经退行性疾病）的方法，我们在动物模型中研究了超高剂量甲钴胺（>1mg/kg/天，I.m.）对 ALS 患者临床症状和生存的影响。已知超高剂量的甲钴胺可以保护神经元免受谷氨酸诱导的兴奋性细胞死亡。使用摇摆小鼠的动物模型研究表明，接受超高剂量甲钴胺治疗的小鼠的生存期显着延长。 SOD1 转基因大鼠的研究仍在进行中，有望产生有益的效果。经德岛大学伦理委员会机构审查委员会批准并获得知情同意后，我们比较了接受该方案治疗的 ALS 患者与未接受该方案治疗的患者的临床症状和生存情况。在对患者的长期随访中，我们证明该方案可显着延长 ALS 患者的生存期。未发现重大不良反应，安全性高。因此，这种方法可能在更大规模的临床试验中被证明是有用的，并且可能为 ALS 提供一种治疗方法。根据本研究的结果，一项临床试验将于今年开始在欧洲启动。我们还通过对运动皮层进行经颅磁刺激来回顾 ALS 的病理生理学，同时受试者最小程度地收缩待测试的肌肉。使用刺激后时间直方图 (PSTH) 分析运动单位放电的时间，刺激后 20-30 毫秒的放电概率激增对应于 EPSP。在 ALS 早期患者中，这种激增与正常人相比显着增强。这与神经兴奋性细胞死亡一致，并且也支持在 ALS 早期给予该方案的疗效。