DEPRENYL/TOCOPHEROL ANTIOXIDATIVE THERAPY OF PARKINSON'S

帕金森病（PD）是一种常见的神经系统疾病， 临床上表现为进行性残疾， 病理学上是通过黑质的减少来实现的 各种 多巴胺能疗法，旨在纠正 黑质变性，在过去的二十年里已经发展起来， 对症治疗PD。 不幸的是，这些疗法 只提供短暂的好处，并由各种各样的 不良影响 实验性疗法正在逐渐转变 针对PD发病机制的预防策略， 更好地了解nigral背后的过程 退化 最近对动物和人类的研究表明， 内源性和外源性氧化机制 PD的发病机制。 试点研究的初步意见 这表明，丙炔苯丙胺，一种相对选择性抑制剂， B型单胺氧化酶和α-生育酚（维生素E）， 具有自由基猝灭能力的抗氧化剂，可以 改善残疾和减缓PD的临床衰退。 我们 对我们进行丙炔苯丙胺和生育酚临床试验的建议 PD的抗氧化治疗是由以下需求引起的： 预防性治疗，一个基于新兴知识的理论基础， 发病机制，试点研究的令人鼓舞的结果， 可行性设计的适用性。 我们假设慢性丙炔苯丙胺和/或α-生育酚 抗氧化疗法将减缓黑色素瘤的进展， 退化和导致的PD临床下降。 我们 初步目的是确定慢性丙炔苯丙胺 和/或生育酚给药至早期，否则未经治疗的PD 患者将延长至需要左旋多巴治疗的时间 来治疗意外残疾 为此，我们提出了一个双重- PD患者的盲态、多机构、前瞻性评价 那些处于疾病早期阶段， 任何对症抗PD治疗。 受试者将由以下人员分配： 使用2 × 2析因设计随机化至四个因子之一 处理：1）丙炔苯丙胺，2）生育酚，3）丙炔苯丙胺加 生育酚，或4）安慰剂。 的主要响应变量 感兴趣的是需要左旋多巴治疗的时间 残疾，最多观察两年。 次要缓解变量包括临床和CSF 与PD进展相关的神经化学指标。

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.