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

Ole A. Andreassen; Robert J. Ferrante; Hsueh Meei Huang; Alpaslan Dedeoglu; Larry Park; Kimberly L. Ferrante; Jennifer Kwon; David R. Borchelt; Christopher A. Ross; Gary E. Gibson; M. Flint Beal

doi:10.1002/ana.1085

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

Ole A. Andreassen, Robert J. Ferrante, Hsueh Meei Huang, Alpaslan Dedeoglu, Larry Park, Kimberly L. Ferrante, Jennifer Kwon, David R. Borchelt, Christopher A. Ross, Gary E. Gibson, M. Flint Beal

School of Medicine

Research output: Contribution to journal › Article › peer-review

61 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	112-116
Number of pages	5
Journal	Annals of neurology
Volume	50
Issue number	1
DOIs	https://doi.org/10.1002/ana.1085
State	Published - 2001

ASJC Scopus subject areas

Neurology
Clinical Neurology

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title = "Dichloroacetate exerts therapeutic effects in transgenic mouse models of Huntington's disease",

abstract = "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.",

author = "Andreassen, {Ole A.} and Ferrante, {Robert J.} and Huang, {Hsueh Meei} and Alpaslan Dedeoglu and Larry Park and Ferrante, {Kimberly L.} and Jennifer Kwon and Borchelt, {David R.} and Ross, {Christopher A.} and Gibson, {Gary E.} and Beal, {M. Flint}",

year = "2001",

doi = "10.1002/ana.1085",

language = "English (US)",

volume = "50",

pages = "112--116",

journal = "Annals of neurology",

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T1 - Dichloroacetate exerts therapeutic effects in transgenic mouse models of Huntington's disease

AU - Andreassen, Ole A.

AU - Ferrante, Robert J.

AU - Huang, Hsueh Meei

AU - Dedeoglu, Alpaslan

AU - Park, Larry

AU - Ferrante, Kimberly L.

AU - Kwon, Jennifer

AU - Borchelt, David R.

AU - Ross, Christopher A.

AU - Gibson, Gary E.

AU - Beal, M. Flint

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

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

Abstract

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