Sodium phenylbutyrate in Huntington's disease: A dose-finding study

Authors

  • Penelope Hogarth MD,

    Corresponding author
    1. Department of Neurology, Oregon Health & Science University, Portland, Oregon, USA
    2. Parkinson's Disease Research, Education & Clinical Center, Portland VA Medical Center, Portland, Oregon, USA
    • Oregon Health & Science University, 3181 SW Sam Jackson Park Road, OP-32, Portland, OR 97239-3098
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  • Luca Lovrecic MD,

    1. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegeneration (MIND), Charlestown, Massachusetts, USA
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  • Dimitri Krainc MD, PhD

    1. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegeneration (MIND), Charlestown, Massachusetts, USA
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Abstract

Transcriptional dysregulation in Huntington's disease (HD) is mediated in part by aberrant patterns of histone acetylation. We performed a dose-finding study in human HD of sodium phenylbutyrate (SPB), a histone deacetylase inhibitor that ameliorates the HD phenotype in animal models. We used a dose-escalation/de-escalation design, using prespecified toxicity criteria and standard clinical and laboratory safety measures. The maximum tolerated dose was 15 g/day. At higher doses, toxicity included vomiting, lightheadedness, confusion, and gait instability. We saw no significant laboratory or electrocardiographic abnormalities. Gene expression changes in blood suggested an inverse dose-response. In conclusion, SPB at 12 to 15 g/day appears to be safe and well-tolerated in human HD. © 2007 Movement Disorder Society

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