BACLOFEN AS PROTECTIVE THERAPY IN HUNTINGTON'S DISEASE

亨廷顿病（HD）是一种明确的遗传性疾病 以神经元变性和进行性残疾为特征。 只 姑息治疗是可行的。 虽然DH的发病机制 尚未完全阐明，纹状体和其他基底神经元群体 神经节区域特别容易受到基因突变的影响。 表情 从HD患者研究中积累证据， 实验动物表明，神经元变性与神经元变性有关。 对谷氨酸敏感性改变介导的毒性过程。 至今没有 临床研究已经评估了是否长期衰减 多巴胺能神经传递可能对神经元变性具有保护作用 从而防止HD患者的持续恶化。 基于巴氯芬减少突触前谷氨酸释放的证据 并且HD中保留了皮质纹状体神经递质通路，我们 进行了一项长期、双盲、安慰剂对照研究， 评估巴氯芬对HD病程的保护作用。 以来 1982年4月，60名处于第一和第二阶段的血液透析患者接受了 评估并随机分配至巴氯芬或安慰剂治疗组。 受试者 每隔6至12个月重新评估临床特征 （功能、运动、认知、精神、代谢测量）， 尾状核萎缩的放射学相关性和 脑脊液 HD的评估程序足够 敏感地检测3年内有意义的临床变化， 观察. 到1987年初，预期的评价将于1999年完成。 我们的整个HD患者队列，以及主要结局变量的分析 将进行。 我们预计，继续开展这一项目将产生：1）a 大量的知识，关于HD的自然历史， 疾病的早期阶段，2）治疗有用的信息，为护理 HD患者及其家属，和3）一个可行的范例， 评估HD的保护性治疗。 如果我们的假设被证实， 巴氯芬将代表HD的第一个实质性治疗， 未来的治疗策略将被衡量。

Huntington's disease (HD) is a well defined hereditary disorder characterized by neuronal degeneration and progressive disability. Only palliative therapies are available. Although the pathogenesis of DH has not been fully clarified, neuronal populations in striatum and other basal ganglia regions are particularly vulnerable to the consequences of gene expression. Accumulating evidence from studies of HD patients and laboratory animals suggests that neuronal degeneration is related to a toxic process mediated by altered sensitivity to glutamate. To date, no clinical studies have assessed whether long-term attenuation of glutamatergic neurotransmission might protect against neuronal degeneration and thereby forestall the relentless deterioration of HD patients. Based on the evidence that baclofen reduces presynaptic glutamate release and that the corticostriatal glutamatergic pathway is preserved in HD, we have undertaken a long-term, double-blind, placebo-controlled study to assess the protective influence of baclofen on the course of HD. Since April 1982, 60 HD patients in stages I and II of illness have been evaluated and randomized to baclofen or placebo treatments. Subjects are re-evaluated at 6- to 12-month intervals in terms of clinical features (functional, motoric, cognitive, psychiatric, metabolic measures), radiographic correlates of caudate atrophy and chemical profile of the cerebrospinal fluid. Assessment procedures for HD are sufficiently sensitive to detect meaningful clinical changes within a 3-year period of observation. By early 1987, prospective evaluations will be completed in our entire cohort of HD patients, and analyses of major outcome variables will be undertaken. We anticipate that continuation of this project will result in: 1) a substantial body of knowledge regarding the natural history of HD in the early stages of illness, 2) therapeutically useful information for the care of HD patients and their families, and 3) a workable paradigm for the assessment of protective therapy in HD. If our hypothesis is confirmed, baclofen will represent the first substantive therapy for HD, by which future therapeutic strategies will be gauged.