COENZYME Q10 IN EARLY PARKINSONS DISEASE

辅酶 Q10 治疗早期帕金森病

• 批准号: 2687789
• 负责人: CLIFFORD W SHULTS
• 金额: $ 74.6万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2687789
• 关键词: Parkinson's disease; antiparkinson drugs; brain disorder chemotherapy; chemoprevention; clinical research; clinical trials; drug screening /evaluation; human subject; human therapy evaluation; mitochondria; neuropsychological tests; pharmacokinetics; psychomotor function; ubiquinone

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.

帕金森病（PD）的特征是持续的 黑质神经元（SNpc）中的多巴胺能神经元， 黑质纹状体功能的持续恶化 多巴胺能系统和运动功能的进行性下降。 没有 治疗已明确显示保护黑质纹状体 多巴胺能系统，即减缓这种渐进性恶化 神经系统 此外，有效的临床试验设计，以探索 潜在保护剂的最大耐受剂量和有效性 还没有得到充分的探索。 在这项研究中，我们将使用 一个新的试验设计，以评估潜在的保护性治疗。 的 PD的原因尚不清楚，但数据表明，复杂的功能障碍 I的线粒体电子传递链和过量产生 氧自由基可能参与多巴胺能神经元的死亡 神经元 辅酶Q10（CoQ 10）是复合物I的电子受体 和有效的抗氧化剂 这些特征表明CoQ 10可能 是治疗PD的有效保护剂。 拟议试点 研究是一项随机、双盲、平行组比较， 剂量辅酶Q10（300，600和1200毫克/天）与安慰剂的患者， 早期PD，不需要左旋多巴治疗。 患者 将被随机分配接受四种治疗中的一种， 跟踪直到他们需要左旋多巴治疗，或 最多16个月。这项研究将涉及三个方面：（1） 试验设计-评估旨在有效 评估潜在的最大耐受剂量和有效性 PD的保护性治疗。(2)安全性、耐受性和吸收 辅酶Q10-扩展我们以前的安全性和耐受性的研究 高剂量辅酶Q10 (3)对临床进展和 线粒体功能-评估辅酶Q10影响线粒体功能的能力 PD和血小板线粒体功能的临床进展。