Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease

Huntington's disease (HD) is a progressive neurodegenerative illness for wh ich there is no effective therapy. We examined whether creatine, which may exert neuroprotective effects by increasing phosphocreatine levels or by st abilizing the mitochondrial permeability transition, has beneficial effects in a transgenic mouse model of HD (line 6/2). Dietary creatine supplementa tion significantly improved survival, slowed the development of brain atrop hy, and delayed atrophy of striatal neurons and the formation of huntingtin -positive aggregates in R6/2 mice. Body weight and motor performance on the rotarod test were significantly improved in creatine-supplemented R6/2 mic e, whereas the onset of diabetes was markedly delayed. Nuclear magnetic res onance spectroscopy showed that creatine supplementation significantly incr eased brain creatine concentrations and delayed decreases in N-acetylaspart ate concentrations. These results support a role of metabolic dysfunction i n a transgenic mouse model of HD and suggest a novel therapeutic strategy t o slow the pathological process.