Author/Editor		Hogarth, P; Lovrečić, L; Krainc, D
Title		Sodium phenylbutyrate in Huntington's disease: a dose-finding study
Type		članek
Source		Mov Disord
Vol. and No.		Letnik 22, št. 13
Publication year		2007
Volume		str. 1962-4
Language		eng
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. (c) 2007 Movement Disorder Society.
Descriptors		HUNTINGTON'S DISEASE HISTONES AMIDOHYDROLASES SODIUM PHENYLBUTYRATES DOSE-RESPONSE RELATIONSHIP, DRUG