Sodium phenylbutyrate in Huntington's disease: a dose-finding study.
Identifieur interne : 002564 ( PubMed/Curation ); précédent : 002563; suivant : 002565Sodium phenylbutyrate in Huntington's disease: a dose-finding study.
Auteurs : Penelope Hogarth [États-Unis] ; Luca Lovrecic ; Dimitri KraincSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2007.
English descriptors
- KwdEn :
- Adult, Aged, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Gene Expression (drug effects), Genetic Markers (genetics), Histone Deacetylase Inhibitors, Humans, Huntington Disease (drug therapy), Huntington Disease (genetics), Lymphocytes (metabolism), Male, Middle Aged, Phenylbutyrates (administration & dosage), Phenylbutyrates (toxicity), Polymerase Chain Reaction, RNA, Messenger (genetics), Sodium (administration & dosage), Sodium (toxicity).
- MESH :
- chemical , administration & dosage : Phenylbutyrates, Sodium.
- chemical , genetics : Genetic Markers, RNA, Messenger.
- drug effects : Gene Expression.
- drug therapy : Huntington Disease.
- genetics : Huntington Disease.
- metabolism : Lymphocytes.
- chemical , toxicity : Phenylbutyrates, Sodium.
- Adult, Aged, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Histone Deacetylase Inhibitors, Humans, Male, Middle Aged, Polymerase Chain Reaction.
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.
DOI: 10.1002/mds.21632
PubMed: 17702032
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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></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">17702032</PMID><DateCreated><Year>2007</Year><Month>11</Month><Day>05</Day></DateCreated><DateCompleted><Year>2008</Year><Month>03</Month><Day>21</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0885-3185</ISSN><JournalIssue CitedMedium="Print"><Volume>22</Volume><Issue>13</Issue><PubDate><Year>2007</Year><Month>Oct</Month><Day>15</Day></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. 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