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: 6162987
• 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/6162987
• 关键词: HIV infections; amyotrophic lateral sclerosis; carbonic anhydrase inhibitors; carnitine; clinical research; clinical trials; dermatomyositis; human subject; human therapy evaluation; hypokalemia; immunity; immunocytochemistry; immunoglobulins; immunotherapy; 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 the etiology (infection, immunity and/or genetics) of chronic diseases of the neuromuscular system and design effective therapies. Current studies involve patients with polymyositis, dermatomyositis, inclusion body myositis, post-polio syndrome, demyelinating polyneuropathies, neuromuscular diseases associated with HIV infection, metabolic myopathies, hypokalemic periodic paralysis, dystrophies, myastenia gravis, diabetic neuropathies and stiff-man syndrome. The pathogenesis of post-polio syndrome is explored with a series of electro- physiological, virological, immunological and histological studies. Persistent or mutant poliovirus is sought in these patient's tissues using tissue cultures, PCR, and in situ hybridization. The mechanism of post-polio fatigue, a common and disabling symptom in many patients, is examined by analysis of the neuroendocrine axis, Magnetic Resonance Spectroscopy and sleep studies. Sequence of the beta-amyloid presursor protein gene was 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 and induced cytokine in the cause of neuropathy or myopathy is investigated with a variety of immunocytochemical studies, in situ hybridization and PCR. The antiretroviral drug ddC was found to cause a unique neuropathy characterized by abnormal mitochondria as determined by various morphological, molecular and biochemical studies. The cytotoxic basis of anti-GAD antibodies in patients with stiff-man syndrome is investigated and changes in the antibody titers are studied in vivo and in vitro and during therapy. Randomized-controlled clinical trials are conducted using high-dose Intravenous immunoglobulin in patients with polymyositis, dermatomyositis, inclusion body myositis, chronic inflammatory and paraproteinemic demyelinating polyneuropathies, stiff-man syndrome, myasthenia gravis and diabetic autoimmune neuropathy. A controlled study using dichlorophenamide, a carbonic anhydrase inhibitor, has been conducted in patients with hypokalemic periodic paralysis. Another controlled study using L-carnitine has been also conducted in patients with AZT-induced mitochondrial myopathy with carnitine depletion.

进行临床和实验室研究以确定病因 慢性疾病（感染、免疫和/或遗传） 神经肌肉系统并设计有效的疗法。目前的研究 涉及多发性肌炎、皮肌炎、包涵体患者 肌炎、脊髓灰质炎后综合症、脱髓鞘性多发性神经病、 与 HIV 感染相关的神经肌肉疾病、代谢性疾病 肌病、低钾性周期性麻痹、营养不良、肌无力 重症肌无力、糖尿病神经病变和僵人综合症。发病机制 通过一系列电子技术探索了脊髓灰质炎后综合症的发病机制 生理学、病毒学、免疫学和组织学研究。 在这些患者的组织中寻找持久性或突变型脊髓灰质炎病毒 使用组织培养、PCR 和原位杂交。 机制 脊髓灰质炎后疲劳是许多患者常见的致残症状， 通过神经内分泌轴分析、磁共振检查 光谱学和睡眠研究。 β-淀粉样蛋白前体的序列 对家族性和散发性患者进行了蛋白质基因检测 包涵体肌炎。神经肌肉疾病的范围 与 HIV 感染的相关性已被研究，并且其作用 病毒和诱导的细胞因子在神经病或肌病的病因中是 通过各种免疫细胞化学研究进行了原位研究 杂交和PCR。抗逆转录病毒药物 ddC 被发现会导致 一种独特的神经病，其特征是线粒体异常（经测定） 通过各种形态学、分子和生物化学研究。 这 僵人患者抗 GAD 抗体的细胞毒性基础 研究综合症并研究抗体滴度的变化 体内和体外以及治疗期间。随机对照临床 使用高剂量静脉注射免疫球蛋白进行的试验 多发性肌炎、皮肌炎、包涵体肌炎患者， 慢性炎症和副蛋白血症性脱髓鞘性多发性神经病， 僵人综合症、重症肌无力和糖尿病自身免疫 神经病。 使用二氯苯酰胺（一种碳酸）的对照研究 脱水酶抑制剂，已在低钾血症患者中进行 周期性麻痹。另一项使用左旋肉碱的对照研究是 还在 AZT 诱导的线粒体肌病患者中进行了 肉碱耗尽。