Exercise adaptations in mitochondrial myopathy: therapeutic implications

线粒体肌病的运动适应:治疗意义

基本信息

  • 批准号:
    7680225
  • 负责人:
  • 金额:
    $ 52.64万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2006
  • 资助国家:
    美国
  • 起止时间:
    2006-09-05 至 2012-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Long term objective: To determine the safety and efficacy of endurance exercise training as therapy and the potentially adverse effects of habitual physical inactivity in patients with skeletal muscle mitochondrial electron transport chain defects due to heteroplasmic mitochondrial DNA mutations. Specific Aims: 1) To establish that in patients with mtDNA defects, endurance training induces mitochondrial proliferation whereby increases in wild-type mtDNA levels offset high levels of mutant mtDNA in individual muscle cells, thereby improving mitochondrial oxidative capacity and ultimately exercise performance and quality of life; and to determine effects of endurance training on cardiac function and capillary formation in skeletal muscle; 2) In these patients, to establish the effects of prolonged physical inactivity (normally associated with down- regulation of mitochondrial volume) on levels of mutant mtDNA and oxidative capacity in muscle and upon cardiac function and capillary levels in skeletal muscle. Research Design: Patients will undergo physiological exercise testing, cardiac evaluation and muscle needle biopsy and then be randomized to regular exercise training or no training for 6 months with retesting at the end of that time; then untrained patients will train and trained patients detrain for 6 months with repeat testing at the end of that time; thereafter, patients will be encouraged to train for an additional 1 year with retesting at the end of that period. Training and detraining effects on mitochondrial genotype and function will be determined by changes in copy number of mutant and wild-type mtDNA; these genetic changes will be correlated with respiratory complex enzymatic activity and assembly in individual muscle cells or homogenate. Training effects on muscle and cardiovascular function will be assessed by monitoring peak work, oxygen utilization, cardiac output and stroke volume in cycle exercise, and by monitors of quality of life. Given the prevalence of mitochondrial myopathies attributable to mitochondrial DNA mutations, the current lack of any effect therapy, and the possible negative effects of physical inactivity on muscle oxidative capacity, there is an immediate need to define appropriate recommendations for exercise training in patients with mitochondrial electron transport chain defects.
描述(由申请人提供):长期目标:确定耐力运动训练作为治疗的安全性和有效性,以及由于骨骼肌线粒体电子传输链缺陷而由于杂质质质神经质性线粒体DNA突变而导致的骨骼肌线粒体电子传输链缺陷的潜在不利影响。具体目的:1)确定在MTDNA缺陷的患者中,耐力训练会诱导线粒体增殖,从而增加野生型mtDNA水平的增加,从而抵消了单个肌肉细胞中高水平的突变MTDNA,从而改善了线粒体氧化能力的能力,并最终锻炼性能,并最终锻炼生命和质量;并确定耐力训练对骨骼肌中心脏功能和毛细血管形成的影响; 2)在这些患者中,为了确定长期不活跃(通常与线粒体体积的下调相关)对突变体mtDNA水平的影响以及肌肉中肌肉的氧化能力,对骨骼肌的心脏功能和毛细血管水平。研究设计:患者将接受生理运动测试,心脏评估和肌肉针头活检,然后在当时结束时进行重新测试,然后在6个月内随机进行定期运动训练;然后,未经训练的患者将在当时结束时训练和训练的患者在重复测试中受到6个月的影响。此后,将鼓励患者在该期间结束时进行重新测试再进行1年的培训。训练和损失对线粒体基因型和功能的影响将取决于突变体和野生型mtDNA的拷贝数的变化;这些遗传变化将与单个肌肉细胞或匀浆中的呼吸复合酶活性和组装相关。训练对肌肉和心血管功能的影响将通过监测峰值工作,氧气利用,心输出量和循环运动中的中风量以及通过监测生活质量来评估。考虑到可归因于线粒体DNA突变的线粒体肌病的患病率,目前缺乏任何效应疗法,以及身体不活跃对肌肉氧化能力的可能负面影响,因此有立即需要定义适当的建议,以在干线电动电子传输链缺陷患者中进行运动训练。

项目成果

期刊论文数量(0)
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RONALD G HALLER其他文献

RONALD G HALLER的其他文献

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{{ truncateString('RONALD G HALLER', 18)}}的其他基金

MITOCHONDRIAL MYOPATHIES AND GLYCOGEN STORAGE DISEASES
线粒体肌病和糖原储存疾病
  • 批准号:
    8363913
  • 财政年份:
    2011
  • 资助金额:
    $ 52.64万
  • 项目类别:
SKELETAL MUSCLE METABOLISM: EXERCISE AND MYOPATHIES
骨骼肌代谢:运动和肌病
  • 批准号:
    8171664
  • 财政年份:
    2010
  • 资助金额:
    $ 52.64万
  • 项目类别:
SKELETAL MUSCLE METABOLISM: EXERCISE AND MYOPATHIES
骨骼肌代谢:运动和肌病
  • 批准号:
    7956986
  • 财政年份:
    2009
  • 资助金额:
    $ 52.64万
  • 项目类别:
Exercise adaptations in mitochondrial myopathy: therapeutic implications
线粒体肌病的运动适应:治疗意义
  • 批准号:
    7144851
  • 财政年份:
    2006
  • 资助金额:
    $ 52.64万
  • 项目类别:
Exercise adaptations in mitochondrial myopathy: therapeutic implications
线粒体肌病的运动适应:治疗意义
  • 批准号:
    7482376
  • 财政年份:
    2006
  • 资助金额:
    $ 52.64万
  • 项目类别:
Exercise adaptations in mitochondrial myopathy: therapeutic implications
线粒体肌病的运动适应:治疗意义
  • 批准号:
    7285269
  • 财政年份:
    2006
  • 资助金额:
    $ 52.64万
  • 项目类别:
Exercise adaptations in mitochondrial myopathy: therapeutic implications
线粒体肌病的运动适应:治疗意义
  • 批准号:
    7934679
  • 财政年份:
    2006
  • 资助金额:
    $ 52.64万
  • 项目类别:
Exercise adaptations in mitochondrial myopathy: therapeutic implications
线粒体肌病的运动适应:治疗意义
  • 批准号:
    8137713
  • 财政年份:
    2006
  • 资助金额:
    $ 52.64万
  • 项目类别:
OXIDATIVE & ANAPLEROTIC FLUX IN NORMAL & METABOLICALLY IMPAIRED SKELETAL MUSCLE
氧化
  • 批准号:
    7180719
  • 财政年份:
    2005
  • 资助金额:
    $ 52.64万
  • 项目类别:
OXIDATIVE AND ANAPLEROTIC FLUX IN SKELETAL MUSCLE
骨骼肌的氧化和回补通量
  • 批准号:
    6977488
  • 财政年份:
    2004
  • 资助金额:
    $ 52.64万
  • 项目类别:

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