Dose ranging and efficacy study of high-dose coenzyme Q10 formulations in Huntington's disease mice.

There is substantial evidence that a bioenergetic defect may play a role in the pathogenesis of Huntington's Disease (HD). A potential therapy for remediating defective energy metabolism is the mitochondrial cofactor, coenzyme Q10 (CoQ10). We have reported that CoQ10 is neuroprotective in the R6/2 transgenic mouse model of HD. Based upon the encouraging results of the CARE-HD trial and recent evidence that high-dose CoQ10 slows the progressive functional decline in Parkinson's disease, we performed a dose ranging study administering high levels of CoQ10 from two commercial sources in R6/2 mice to determine enhanced efficacy. High dose CoQ10 significantly extended survival in R6/2 mice, the degree of which was dose- and source-dependent. CoQ10 resulted in a marked improvement in motor performance and grip strength, with a reduction in weight loss, brain atrophy, and huntingtin inclusions in treated R6/2 mice. Brain levels of CoQ10 and CoQ9 were significantly lower in R6/2 mice, in comparison to wild type littermate control mice. Oral administration of CoQ10 elevated CoQ10 plasma levels and significantly increased brain levels of CoQ9, CoQ10, and ATP in R6/2 mice, while reducing 8-hydroxy-2-deoxyguanosine concentrations, a marker of oxidative damage. We demonstrate that high-dose administration of CoQ10 exerts a greater therapeutic benefit in a dose dependent manner in R6/2 mice than previously reported and suggest that clinical trials using high dose CoQ10 in HD patients are warranted.