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

Penelope Hogarth, Luca Lovrecic, Dimitri Krainc

Research output: Contribution to journalArticle

64 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1962-1964
Number of pages3
JournalMovement Disorders
Volume22
Issue number13
DOIs
StatePublished - Oct 15 2007

Keywords

  • Histone deacetylase inhibitor
  • Huntington's disease
  • Sodium phenylbutyrate

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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