Energy metabolism defects in Huntington's disease and effects of coenzyme Q10

Authors

  • Walter J. Koroshetz MD,

    1. Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA
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  • Bruce G. Jenkins PhD,

    1. MGH-NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
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  • Bruce R. Rosen MD, PhD,

    1. MGH-NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
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  • Dr M. Flint Beal MD

    Corresponding author
    1. Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA
    • Neurology Service/WRN 408, Massachusetts General Hospital, 32 Fruit Street, Boston, MA 02114
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Abstract

We investigated whether the Huntington's desease (HD) gene mutation may produce either primary or secondary effects on energy metalbolism. 31P magnetic resonance spectroscopy demonstrated a significant decrease in the phosphocreatine to inorganic phosphate ratio in resting muscle of 8 patients as compared with 8 control subjects. The cerebrospinal fluid lactate-pyruvate ratio was significantly increased in 15 patients as compared with 13 control subjects. Lactate concentrations assessed using 1H magnetic resonance spectroscopy are increased in Huntington's disease cerebral cortex. Treatment with coenzyme Q10, an essential cofactor of the electron transport chain, resulted in significant decreases in cortical lactate concentrations in 18 patients, which reversed following withdrawal of therapy. These findings provide evidence for a generalized energy defect in Huntington's disease, and suggest a possible therapy.

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