DEPRENYL/TOCOPHEROL ANTIOXIDATIVE THERAPY OF PARKINSON'S

帕金森病(PD)是一种常见的神经系统疾病， 临床上以进行性残疾和 从病理学上讲，这是由于推进了黑质的丢失。各种各样的 多巴胺能疗法，旨在纠正 黑质变性是在过去的二十年里发展起来的 对帕金森病进行对症治疗。不幸的是，这些疗法 只提供短暂的好处，并由各种 不良影响。实验疗法正在逐渐转变 针对帕金森病发病机制的预防策略 更好地了解黑质的潜在过程 退化。 最近在动物和人类上的研究表明， 细胞内源性和外源性氧化机制的研究 帕金森病的发病机制。来自试点研究的初步观察 提示丙戊烯，一种相对选择性较高的药物 B型单胺氧化酶和α-生育酚(维生素E)，以及 具有自由基猝灭能力的抗氧化剂，可 改善残疾，延缓帕金森病的临床下降。我们的 关于丙戊烯和生育酚临床试验的建议 帕金森病的抗氧化治疗是由于需要 预防性治疗，一种基于新兴知识的理论基础 发病机制，先导研究令人鼓舞的结果，以及 可行性设计的适用性。 我们假设慢性肾上腺素和/或α-生育酚 抗氧化治疗将延缓进行性黑质 帕金森病的退行性变和由此导致的临床衰退。我们的 初步目标是确定慢性丙戊烯 和/或生育酚治疗早期未治疗的帕金森病 患者将延长治疗时间，直到需要左旋多巴治疗。 用来治疗严重的残疾。为此，我们建议实施一项双重- 对PD患者进行盲法、多机构、前瞻性评估 谁处于疾病的最早阶段，谁没有接受 任何有症状的抗帕金森病疗法。科目将由以下人员分配 使用2x2析因设计的随机化到四 治疗：1)丙戊烯，2)生育酚3)丙戊烯加 生育酚或安慰剂。的主要响应变量 利息是需要左旋多巴疗法来治疗的时间 残疾，最长可观察两年。 次要反应变量包括临床和脑脊液 与帕金森病进展相关的神经化学措施。

Parkinson's disease (PD) is a common neurological disorder, characterized clinically by progressive disability and pathologically by advancing nigral loss. A variety of dopaminergic therapies, aimed at rectifying the consequences of nigral degeneration, have been developed in the past two decades for symptomatic treatment of PD. Unfortunately, these therapies provide only transient benefit and are attended by a variety of adverse effects. Experimental therapeutics is gradually shifting to preventative strategies aimed at the pathogenesis of PD as we gain a better understanding of the process underlying nigral degeneration. Recent studies in animals and humans implicate toxicity from endogenous and exogenous oxidative mechanisms in the pathogenesis of PD. Preliminary observations from pilot studies suggest that deprenyl, a relatively selective inhibitor of monoamine oxidase type B, and alpha-tocopherol (vitamin E), an antioxidant with free-radical quenching capacities, may ameliorate disability and slow the clinical decline of PD. Our proposal for our clinical trial of deprenyl and tocopherol antioxidative therapies in PD is prompted by the need for preventive therapies, a rationale based on emerging knowledge of pathogenesis, the encouraging results of pilot studies, and the applicability of a feasible design. We hypothesize that chronic deprenyl and/or alpha-tocopherol antioxidative therapies will slow the progressive nigral degeneration and resulting clinical decline of PD. Our preliminary aim is to determine whether or not chronic deprenyl and/or tocopherol administration to early, otherwise untreated PD patients will prolong the time until levodopa therapy is required to treat supervening disability. To this end, we propose a double- blind, multi-institutional, prospective evaluation of PD patients who are in the earliest stages of illness and who are not receiving any symptomatic anti-PD therapies. Subjects will be assigned by randomization using a 2 x 2 factorial design to one of four treatments: 1) deprenyl, 2) tocopherol 3) deprenyl plus tocopherol, or 4) placebo. The primary response variable of interest is the time until levodopa therapy is required to treat disability, up to a maximum of two years of observation. Secondary response variables include clinical and CSF neurochemical measures relevant to the progression of PD.