COENZYME Q10 IN EARLY PARKINSONS DISEASE

帕金森氏病(PD)的特征是持续丢失 黑质致密部多巴胺能神经元(SNPC)， 黑质纹状体功能持续恶化 多巴胺能系统与运动功能进行性下降。不是 治疗已被确凿地证明能保护黑质纹状体 多巴胺能系统，即减缓这一过程的进展恶化 神经系统。此外，还需要探索临床试验的有效设计 潜在保护剂的最大耐受量和效力 还没有得到充分的勘探。在拟议的研究中，我们将使用 一种新的试验设计来评估潜在的保护性疗法。这个 帕金森病的病因(S)不明，但资料表明，复合体功能障碍 线粒体电子传输链I与过量生产 氧自由基可能参与了多巴胺能神经元的死亡 神经元。辅酶Q10(CoQ10)是配合物I的电子受体 和一种有效的抗氧化剂。这些特征表明，CoQ10可能 在帕金森病的治疗中是一种有用的保护剂。拟议的试点 研究是随机、双盲、平行组的三组比较 服用辅酶Q10(300、600和1200 mg/天)与安慰剂的患者 有早期帕金森病，还不需要左旋多巴治疗。病人 将被随机分配接受四种治疗中的一种 直到他们需要用左旋多巴或 最长为16个月。这项研究将涉及三个方面：(1) 试验设计-评估设计为高效的临床试验设计 评估潜在的最大耐受量和疗效 帕金森病的保护性治疗。(2)安全性、耐受性和吸收率 CoQ10-扩展我们之前对阿司匹林安全性和耐受性的研究 高剂量辅酶Q10。(3)对临床进展的影响和 线粒体功能-评估辅酶Q10影响线粒体功能的能力 帕金森病与血小板线粒体功能的临床进展

Parkinson's disease (PD) is characterized by ongoing loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), continuing deterioration in the function of the nigrostriatal dopaminergic system and progressive decline of motor function. No therapy has been shown conclusively to protect the nigrostriatal dopaminergic system, i.e. slow the progressive deterioration of this neural system. Also, efficient designs of clinical trials to explore the maximally tolerated dose and efficacy of potential protective agents have not been adequately explored. In the proposed study, we will use a novel trial design to evaluate a potential protective therapy. The cause(s) of PD is unknown, but data indicate that dysfunction of complex I of the mitochondrial electron transport chain and excessive production of oxygen free radicals may be involved in the death of dopaminergic neurons. Coenzyme Q10 (CoQ10) is the electron acceptor for complex I and a potent antioxidant. These characteristics suggest that CoQ10 may be a useful protective agent in the treatment of PD. The proposed pilot study is a randomized, double-blind, parallel group comparison of three doses of CoQ10(300, 600 and 1200 mg/day) versus placebo in patients who have early PD and do not yet require treatment with levodopa. Patients will be randomly assigned to receive one of the four treatments and will be followed until the point that they need treatment with levodopa or for a maximum of 16 months. The study will address three areas: (1) Trial Design - Assess a clinical trial design devised to efficiently evaluate the maximally tolerated dose and efficacy of potential protective therapies for PD. (2) Safety, Tolerability and Absorption of CoQ10 - Extend our previous studies of the safety and tolerability of high doses of CoQ10. (3) Effects on Clinical Progression and Mitochondrial Function - Evaluate the ability of CoQ10 to affect the clinical progression of PD and platelet mitochondrial function.