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.
| Shetty, A K; Turner, D A (1999) Vulnerability of the dentate gyrus to aging and intracerebroventricular administration of kainic acid. Exp Neurol 158:491-503 |
