Coenzyme Q10 is a strong antioxidant and an essential quinone intermediate in the mitochondrial electron transport chain, passing electrons from complex I to complexes II and III. Because disruption of the electron transport chain can cause Parkinson-like disease in humans and in mice (see ARF related news story), CoQ10 has been viewed as a potential treatment for the disease. The idea is that by improving electron flow through the respiratory chain, CoQ10 may prevent the formation of reactive oxygen species (ROS), which form when electrons bypass the respiratory chain and react directly with oxygen. ROS are toxic to neurons and have been implicated in the pathology of Parkinson’s and other neurodegenerative diseases, including Alzheimer’s. CoQ10 is also a cofactor for electron transport chain uncouplers, compounds that may prevent generation of ROS by accelerating electron transport (see ARF related news story). Beal and colleagues showed that CoQ10 protects dopaminergic neurons in a mouse model of Parkinson disease based on the mitochondrial toxin MPTP (see Beal et al., 1998).

To test whether CoQ10 can improve symptoms in patients with PD, Storch and colleagues randomly assigned 131 patients to a daily placebo or 300 mg of the supplement in a nanoparticular suspension. This CoQ10 formulation seems to be better absorbed from the intestine and leads to similar plasma levels as do 1,200 mg of the standard preparation. The volunteers were scored in the activities of daily living and motor components of the Unified Parkinson’s Disease Rating Scale (UPDRS) monthly from baseline (1 month prior to treatment start) until the end of treatment (3 months) and again 2 months later. Fifty-five of 67 patients assigned placebo completed the trial, as did 51 of 64 taking the supplement. The researchers found that there was no significant difference in scores between the placebo and treatment group at any time point during the trial. Likewise, there were no significant differences on six secondary outcome measures, including the total UPDRS score.

“Since we did not find symptomatic effects of CoQ10 in PD, our study does not support the hypothesis that restoring the impaired energy metabolism of the disease’s dopaminergic neurons leads to symptomatic benefits in PD,” write the authors. Storch and colleagues deliberately chose a short treatment period to preclude disease progression interfering with the outcome. The duration would also likely be too short to measure any disease-modifying effect of CoQ10. In contrast, the QE3 trial is slated to run for 5 years, and it aims to test patients who are at the very earliest stages of the disease and, unlike the German cohorts, take no other PD medications.

The difference in design of the German Coenzyme Q10 Study Group trial and the QE3 speaks to an important goal in the management of neurodegenerative diseases, i.e., disease modification. In contrast to drugs that alleviate symptoms but do not affect the underlying pathogenic process, such as dopamine agonists for Parkinson’s and acetylcholinesterase inhibitors for Alzheimer’s, sought-after disease-modifying agents would slow or halt progression. “Because there is no surrogate marker for Parkinson disease progression, we have to follow patients clinically using the UPDRS. One of the big criticisms of the QE3 trial was that if CoQ10 has a symptomatic effect, if it boosts mitochondrial metabolism, for example, then its effect may be nothing to do with protection of the brain,” said Henchcliffe. That the German trial found no short-term symptomatic effect appears to address that criticism, but it remains to be seen whether the longer CoQ10 trial proves to have any benefit, disease-modifying or otherwise. The QE3 trial is slated to being recruitment this September.—Tom Fagan.

Reference:
Storch A, Jost WH, Vieregge P, Spiegel J, Greulich W, Durner J, Muller T, Kupsch A, Henningsen H, Oertel WH, Fuchs G, Kuhn W, Niklowitz P, Koch R, Herting B, Reichmann H, for the German Coenzyme Q10 Study Group. Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q10 in Parkinson disease. Archives of Neurology. 2007, May 14. Online publication. Abstract