Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington's disease

RJ Ferrante, OA Andreassen, A Dedeoglu… - Journal of …, 2002 - Soc Neuroscience
RJ Ferrante, OA Andreassen, A Dedeoglu, KL Ferrante, BG Jenkins, SM Hersch, MF Beal
Journal of Neuroscience, 2002Soc Neuroscience
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 …
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 a ∼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.
Soc Neuroscience