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 language | English (US) |
|---|---|
| Pages (from-to) | 1962-1964 |
| Number of pages | 3 |
| Journal | Movement Disorders |
| Volume | 22 |
| Issue number | 13 |
| DOIs | |
| State | Published - Oct 15 2007 |
Keywords
- Histone deacetylase inhibitor
- Huntington's disease
- Sodium phenylbutyrate
ASJC Scopus subject areas
- Neurology
- Clinical Neurology