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:
  • 金额:
    $ 2.11万
  • 依托单位:
  • 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.
为了建立一种治疗肌萎缩侧索硬化症(ALS)的方法,我们研究了超大剂量甲钴胺(>1 mg/kg/day,I.M.)的治疗效果。对肌萎缩侧索硬化症患者的临床症状和动物模型存活的影响。众所周知,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。用Wobbler小鼠进行的动物模型研究表明,服用超高剂量甲钴胺的人存活时间明显延长。SOD1转基因大鼠的研究仍在进行中,有望产生有益的效果。在获得德岛大学伦理委员会机构审查委员会的批准并获得知情同意后,我们比较了接受方案治疗的ALS患者和未接受方案治疗的ALS患者的临床体征和生存情况。在对患者的长期随访中,我们证明了该方案显著延长了ALS患者的生存时间。没有发现重大不良反应,安全性被证实是高的。因此,这种方法可能在更大的临床试验中被证明是有用的,并可能为ALS提供一种治疗方法。作为这项研究的结果,一项临床试验将从今年开始在欧洲启动。我们还回顾了ALS的病理生理学,当受试者最小限度地收缩被测试的肌肉时,通过运动皮质进行经颅磁刺激。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毫秒的放电概率峰对应于EPSP。在ALS早期患者中,与正常人相比,这一峰明显增强。这与神经兴奋性细胞死亡是一致的,也支持了如果在ALS的早期阶段给予该方案的疗效。

项目成果

期刊论文数量(56)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Oga T: "Abnormal cortical mechanisms of voluntary muscle relaxation in patients with writer's cramp : an fMRI study."Brain. 125(Pt 4). 895-903 (2002)
Oga T:“作家痉挛患者随意性肌肉松弛的异常皮质机制:一项功能磁共振成像研究。”大脑。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Kaji R: "Physiology of conduction block in multifocal motor neuropathy and other demyelinating neuropathies"Muscle Nerve.. 27(3). 285-296 (2003)
Kaji R:“多灶性运动神经病和其他脱髓鞘性神经病中传导阻滞的生理学”肌肉神经.. 27(3)。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Kiernan MC: "Evidence for axonal membrane hyperpolarrization in multifocal motor neuropathy with conduction block."Brain. 125(Pt 3). 664-675 (2002)
Kiernan MC:“传导阻滞多灶性运动神经病中轴突膜超极化的证据。”大脑。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Hattori N: "Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32) : a clinicopathological study of 205 Japanese patients."Brain. 126(pt 1). 134-151 (2003)
Hattori N:“伴有髓磷脂相关蛋白(PMP22、MPZ 和 Cx32)突变的腓骨肌萎缩症的脱髓鞘和轴突特征:对 205 名日本患者进行的临床病理学研究。” 大脑。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Kohara N: "Pathophysiology of weakness in a patient with congenital end-plate acetylcholinesterase deficiency"Muscle & Nerve. 25(4). 585-592 (2002)
Kohara N:“先天性终板乙酰胆碱酯酶缺乏症患者无力的病理生理学”肌肉
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

KAJI Ryuji其他文献

KAJI Ryuji的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('KAJI Ryuji', 18)}}的其他基金

Research on molecular pathogenesis and next-generation therapeutic agent for dystonia-parkinsonism
肌张力障碍-帕金森症的分子发病机制及新一代治疗药物的研究
  • 批准号:
    24390223
  • 财政年份:
    2012
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Development of a novel therapeutic approach for ALS using anti-TNF antibody
使用抗 TNF 抗体开发 ALS 新型治疗方法
  • 批准号:
    23659458
  • 财政年份:
    2011
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Translational study of molecular pathogenesis on dystonia and developing its novel therapeutic interventions
肌张力障碍分子发病机制的转化研究及其新的治疗干预措施
  • 批准号:
    21390269
  • 财政年份:
    2009
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
AmuIti-disciplinary approach to the genesis and therapy for dystonia
肌张力障碍的起源和治疗的多学科方法
  • 批准号:
    18390260
  • 财政年份:
    2006
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
A study on pahtophysiology and non-invasive treatment of dystonia
肌张力障碍的病理生理学及无创治疗研究
  • 批准号:
    15390274
  • 财政年份:
    2003
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Physiological Study on Conduction Block and anti GM1 Antibody in Multifocal Motor Neuropathy
传导阻滞和抗GM1抗体在多灶性运动神经病中的生理学研究
  • 批准号:
    12672356
  • 财政年份:
    2000
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Effect of Lymphokine on Saltatory Nerve Conduction in Single Myelinated Nerve Fibers.
淋巴因子对单髓神经纤维跳跃神经传导的影响。
  • 批准号:
    06670651
  • 财政年份:
    1994
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
Effect of Na-K exchanger inhibitor bepridil on neuronal death -single fiber study-
Na-K交换抑制剂贝普地尔对神经元死亡的影响-单纤维研究-
  • 批准号:
    04670487
  • 财政年份:
    1992
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)

相似海外基金

Facial nerve regeneration with using a nanofiber sheet incorporating methylcobalamin,
使用含有甲钴胺的纳米纤维片进行面神经再生,
  • 批准号:
    18K09346
  • 财政年份:
    2018
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
DNA Methyltransferase Target Sites in Cancer
癌症中的 DNA 甲基转移酶靶位点
  • 批准号:
    8527000
  • 财政年份:
    2013
  • 资助金额:
    $ 2.11万
  • 项目类别:
DNA Methyltransferase Target Sites in Cancer
癌症中的 DNA 甲基转移酶靶位点
  • 批准号:
    8775601
  • 财政年份:
    2013
  • 资助金额:
    $ 2.11万
  • 项目类别:
Analysis of Proline Isomerization in Epigenetics
表观遗传学中脯氨酸异构化分析
  • 批准号:
    8658810
  • 财政年份:
    2012
  • 资助金额:
    $ 2.11万
  • 项目类别:
Analysis of Proline Isomerization in Epigenetics
表观遗传学中脯氨酸异构化分析
  • 批准号:
    8453524
  • 财政年份:
    2012
  • 资助金额:
    $ 2.11万
  • 项目类别:
Polymorphisms of estrogen-metabolizing genes in kidney cancer
肾癌雌激素代谢基因多态性
  • 批准号:
    8046990
  • 财政年份:
    2011
  • 资助金额:
    $ 2.11万
  • 项目类别:
Polymorphisms of estrogen-metabolizing genes in kidney cancer
肾癌雌激素代谢基因多态性
  • 批准号:
    8696771
  • 财政年份:
    2011
  • 资助金额:
    $ 2.11万
  • 项目类别:
Polymorphisms of estrogen-metabolizing genes in kidney cancer
肾癌雌激素代谢基因多态性
  • 批准号:
    8397558
  • 财政年份:
    2011
  • 资助金额:
    $ 2.11万
  • 项目类别:
Polymorphisms of estrogen-metabolizing genes in kidney cancer
肾癌雌激素代谢基因多态性
  • 批准号:
    8245581
  • 财政年份:
    2011
  • 资助金额:
    $ 2.11万
  • 项目类别:
Messenger RNA Capping and Methylation in Pneumoviruses
肺病毒中的信使 RNA 加帽和甲基化
  • 批准号:
    8050356
  • 财政年份:
    2010
  • 资助金额:
    $ 2.11万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了