Dichloroacetate exerts therapeutic effects in transgenic mouse models of Huntington's disease

Dichloroacetate (DCA) stimulates pyruvate dehydrogenase complex (PDHC) acti vity and lowers cerebral lactate concentrations. In the R6/2 and N171-82Q t ransgenic mouse models of Huntington's disease (HD), DCA significantly incr eased survival, improved motor function, delayed loss of body weight, atten uated the development of striatal neuron atrophy, and prevented diabetes. T he percentage of PDHC in the active form was significantly reduced in R6/2 mice at 12 weeks of age, and DCA ameliorated the deficit. These results pro vide further evidence for a role of energy dysfunction in HD pathogenesis a nd suggest that DCA may exert therapeutic benefits in HD.