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: 3782296
• 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/3782296
• 关键词: HIV infections; amyotrophic lateral sclerosis; biopsy; carnitine; chronic disease /disorder; clinical trials; dermatomyositis; human immunodeficiency virus; human subject; human therapy evaluation; human tissue; immunity; immunocytochemistry; immunoglobulins; in situ hybridization; 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 electrophysiologic, virologic, immunologic and histologic 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 under study. 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 an unique myopathy characterized by abnormal mitochondria as determined by various morphologic, 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. Because patients with AZT~myopathy have low muscle carnitine, a controlled clinical trial using oral L~ carnitine is now conducted. 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