Therapeutic Effects of Coenzyme Q₁₀and Remacemide in Transgenic Mouse Models of Huntington's Disease

TLDR

Bioenergetic defects and excitotoxicity are implicated in Huntington’s disease pathogenesis. The study evaluates oral coenzyme Q10 and the NMDA antagonist remacemide to target impaired energy metabolism and excitotoxicity. In R6/2 and N171‑82Q mice, each drug alone extended survival and delayed motor and neuropathological deficits, while combined treatment increased survival by ~32% and 17% and reduced ventricular enlargement, underscoring the therapeutic potential of targeting energy metabolism and excitotoxicity.

Abstract

There is substantial evidence that bioenergetic defects and excitotoxicity may play a role in the pathogenesis of Huntington's disease (HD). Potential therapeutic strategies for neurodegenerative diseases in which there is reduced energy metabolism and NMDA-mediated excitotoxicity are the administration of the mitochondrial cofactor coenzyme Q10 and the NMDA antagonist remacemide. We found that oral administration of either coenzyme Q10 or remacemide significantly extended survival and delayed the development of motor deficits, weight loss, cerebral atrophy, and neuronal intranuclear inclusions in the R6/2 transgenic mouse model of HD. The combined treatment, using coenzyme Q10 and remacemide together, was more efficacious than either compound alone, resulting in an approximately 32 and 17% increase in survival in the R6/2 and N171-82Q mice, respectively. Magnetic resonance imaging showed that combined treatment significantly attenuated ventricular enlargement in vivo. These studies further implicate defective energy metabolism and excitotoxicity in the R6/2 and N171-82Q transgenic mouse models of HD and are of interest in comparison with the outcome of a recent clinical trial examining coenzyme Q10 and remacemide in HD patients.