Dose ranging and efficacy study of high-dose coenzyme Q 10 formulations in Huntington's disease mice

Abstract

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 Q 10 (CoQ 10). We have reported that CoQ 10 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 CoQ 10 slows the progressive functional decline in Parkinson's disease, we performed a dose ranging study administering high levels of CoQ 10 from two commercial sources in R6/2 mice to determine enhanced efficacy. High dose CoQ 10 significantly extended survival in R6/2 mice, the degree of which was dose- and source-dependent. CoQ 10 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 CoQ 10 and CoQ 9 were significantly lower in R6/2 mice, in comparison to wild type littermate control mice. Oral administration of CoQ 10 elevated CoQ 10 plasma levels and significantly increased brain levels of CoQ 9, CoQ 10, 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 CoQ 10 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 CoQ 10 in HD patients are warranted.