Dichloroacetate exerts therapeutic effects in transgenic mouse models of Huntington's disease.
Dichloroacetate (DCA) stimulates pyruvate dehydrogenase complex (PDHC) activity and lowers cerebral lactate concentrations. In the R6/2 and N171-82Q transgenic mouse models of Huntington's disease (HD), DCA significantly increased survival, improved motor function, delayed loss of body weight, attenuated the development of striatal neuron atrophy, and prevented diabetes. The 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 provide further evidence for a role of energy dysfunction in HD pathogenesis and suggest that DCA may exert therapeutic benefits in HD.
Andreassen
O A
OA
Neurochemistry Laboratory, Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
Ferrante
R J
RJ
Huang
H M
HM
Dedeoglu
A
A
Park
L
L
Ferrante
K L
KL
Kwon
J
J
Borchelt
D R
DR
Ross
C A
CA
Gibson
G E
GE
Beal
M F
MF
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003999:Dichloroacetic Acid / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D013997:Time Factors
D003999:Dichloroacetic Acid