COMBINED CLINICAL, VIRAL, AND IMMUNOLOGICAL STUDIES OF NEUROMUSCULAR DISEASES

神经肌肉疾病的临床、病毒和免疫学综合研究

• 批准号: 5203885
• 负责人: M C DALAKAS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5203885
• 关键词: HIV infections; amyotrophic lateral sclerosis; carbonic anhydrase inhibitors; carnitine; clinical trials; dermatomyositis; human immunodeficiency virus; human subject; human therapy evaluation; human tissue; hypokalemia; immunity; immunocytochemistry; immunoglobulins; longitudinal human study; muscular dystrophy; myelinopathy; neuromuscular disorder; neuromuscular disorder chemotherapy; paralysis; pathologic process; poliomyelitis; polymerase chain reaction; polymyositis; zidovudine

Clinical and laboratory studies are conducted to determine etiology (infection, immunity and/or genetics) of chronic diseases of the neuromuscular system and design effective therapies. Current studies involve patients with polymyositis/dermatomyositis, post-polio syndrome, amyotrophic lateral sclerosis (ALS), demyelinating polyneuropathies, neuromuscular diseases associated with HIV infection, hypokalemic periodic paralysis and Duchenne muscular dystrophy. The pathogenesis of post-polio syndrome is explored with a series of electrophysiological, virological, immunological and histological studies. The findings are compared with those seen in patients with acute paralytic poliomyelitis and other motor neuron diseases. Persistent or mutant poliovirus is sought in these patients' tissues using tissue cultures, PCR, and in situ hybridization. Because abnormal immunoregulation was found in some patients, a double-blind placebo-controlled trial using prednisone was conducted. The mechanism of post-polio fatigue, a common and disabling symptom in many patients, is examined by analysis of the neuroendocrine axis and by magnetic resonance spectroscopy. Sequence of the beta amyloid precursor protein gene is performed in patients with familial and sporadic inclusion body myositis. The spectrum of neuromuscular disorders associated with HIV infection has been studied and the role of the virus in the cause of neuropathy or myopathy is investigated with a variety of immunocytochemical studies, in situ hybridization and PCR. The antiretroviral drug AZT was found to cause a unique myopathy characterized by abnormal mitochondria as determined by various morphological, molecular, biochemical and immunocytochemical studies. A longitudinal study of HIV-positive patients that develop myopathic symptoms while on AZT is conducted with serial muscle biopsies to assess factors associated with the development of myopathy. Patients with AZT- myopathy were found to have low muscle carnitine level. This has prompted the conduction of an ongoing randomized controlled clinical trial using oral L- carnitine. Randomized-controlled clinical trials are conducted with high-dose Intravenous immunoglobulin in patients with polymyositis/dermatomyositis, chronic inflammatory and paraproteinemic demyelinating polyneuropathies, ALS, and Duchenne muscular dystrophy. A controlled study using dichlorophenamide, a carbonic anhydrase inhibitor, is also conducted in patients with hypokalemic periodic paralysis.

进行临床和实验室研究以确定病因 （感染、免疫力和/或遗传学） 神经肌肉系统和设计有效的治疗方法。目前的研究 涉及患有多发性肌炎/皮肌炎、脊髓灰质炎后综合征 肌萎缩侧索硬化症（ALS），脱髓鞘性多发性神经病， 与HIV感染相关的神经肌肉疾病，低钾血症 周期性麻痹和杜氏肌营养不良症。的发病机制 脊髓灰质炎后综合征是用一系列电生理学， 病毒学、免疫学和组织学研究。 这些发现是 与急性麻痹性脊髓灰质炎患者相比， 和其他运动神经元疾病。 持续性或突变型脊髓灰质炎病毒是 在这些患者的组织中使用组织培养，PCR和原位杂交， 杂交方法因为在一些人中发现了异常的免疫调节， 患者，使用泼尼松的双盲安慰剂对照试验， 进行。脊髓灰质炎后疲劳的机制，一种常见的和致残的 许多患者的症状，是通过分析神经内分泌检查 轴和磁共振光谱。 Beta的顺序 淀粉样前体蛋白基因在家族性和 散发性包涵体肌炎。 神经肌肉频谱 与艾滋病毒感染有关的疾病已经研究， 病毒在神经病或肌病的原因是调查与 各种免疫细胞化学研究，原位杂交和PCR。 抗逆转录病毒药物AZT被发现会导致一种独特的肌病 其特征在于通过各种方法确定的异常线粒体 形态学、分子生物学和免疫细胞化学研究。一 对发生肌病的HIV阳性患者的纵向研究 症状，而对AZT是进行了一系列肌肉活检，以评估 与肌病发展相关的因素。 AZT患者- 发现肌病患者肌肉肉毒碱水平较低。 这 促使进行一项正在进行的随机对照临床试验， 使用口服左旋肉碱的试验。随机对照临床试验是 高剂量静脉注射免疫球蛋白， 慢性炎症性和副蛋白血症性多发性肌炎/皮肌炎 脱髓鞘性多发性神经病、ALS和杜氏肌营养不良。一 使用二氯苯甲酰胺，一种碳酸酐酶抑制剂， 也在低钾性周期性麻痹患者中进行。