Sodium phenylbutyrate in huntington's disease : A dose-finding study
Identifieur interne : 001457 ( PascalFrancis/Checkpoint ); précédent : 001456; suivant : 001458Sodium phenylbutyrate in huntington's disease : A dose-finding study
Auteurs : Penelope Hogarth [États-Unis] ; Luca Lovrecic [États-Unis] ; Dimitri Krainc [États-Unis]Source :
- Movement disorders [ 0885-3185 ] ; 2007.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Sodium.
English descriptors
- KwdEn :
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.
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<front><div type="abstract" xml:lang="en">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.</div>
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