MovDisordV3, Main, Curation, bibRecord, 002B67

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

Identifieur interne : 002B67 ( Main/Curation ); précédent : 002B66; suivant : 002B68

Sodium 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 ] ; 2007-10-15.

RBID : ISTEX:6FF31B34BBC74B3B9081F504D87EED5D30419A26

Descripteurs français

Pascal (Inist)
- Chorée de Huntington, Pathologie du système nerveux, Sodium.
Wicri :
- topic : Sodium.

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), Huntington disease, Huntington's disease, Lymphocytes (metabolism), Male, Middle Aged, Nervous system diseases, Phenylbutyrates (administration & dosage), Phenylbutyrates (toxicity), Polymerase Chain Reaction, RNA, Messenger (genetics), Sodium, Sodium (administration & dosage), Sodium (toxicity), histone deacetylase inhibitor, sodium phenylbutyrate.
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. © 2007 Movement Disorder Society

Url:

https://api.istex.fr/document/6FF31B34BBC74B3B9081F504D87EED5D30419A26/fulltext/pdf

DOI: 10.1002/mds.21632

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Le document en format XML

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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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<affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegeneration (MIND), Charlestown, Massachusetts</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
</analytic>
<monogr></monogr>
<series><title level="j">Movement Disorders</title>
<title level="j" type="abbrev">Mov. Disord.</title>
<idno type="ISSN">0885-3185</idno>
<idno type="eISSN">1531-8257</idno>
<imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher>
<pubPlace>Hoboken</pubPlace>
<date type="published" when="2007-10-15">2007-10-15</date>
<biblScope unit="vol">22</biblScope>
<biblScope unit="issue">13</biblScope>
<biblScope unit="page" from="1962">1962</biblScope>
<biblScope unit="page" to="1964">1964</biblScope>
</imprint>
<idno type="ISSN">0885-3185</idno>
</series>
<idno type="istex">6FF31B34BBC74B3B9081F504D87EED5D30419A26</idno>
<idno type="DOI">10.1002/mds.21632</idno>
<idno type="ArticleID">MDS21632</idno>
</biblStruct>
</sourceDesc>
<seriesStmt><idno type="ISSN">0885-3185</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Dose-Response Relationship, Drug</term>
<term>Drug Administration Schedule</term>
<term>Female</term>
<term>Gene Expression (drug effects)</term>
<term>Genetic Markers (genetics)</term>
<term>Histone Deacetylase Inhibitors</term>
<term>Humans</term>
<term>Huntington Disease (drug therapy)</term>
<term>Huntington Disease (genetics)</term>
<term>Huntington's disease</term>
<term>Lymphocytes (metabolism)</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Phenylbutyrates (administration & dosage)</term>
<term>Phenylbutyrates (toxicity)</term>
<term>Polymerase Chain Reaction</term>
<term>RNA, Messenger (genetics)</term>
<term>Sodium (administration & dosage)</term>
<term>Sodium (toxicity)</term>
<term>histone deacetylase inhibitor</term>
<term>sodium phenylbutyrate</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Phenylbutyrates</term>
<term>Sodium</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Genetic Markers</term>
<term>RNA, Messenger</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Gene Expression</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Huntington Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Huntington Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lymphocytes</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Phenylbutyrates</term>
<term>Sodium</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Dose-Response Relationship, Drug</term>
<term>Drug Administration Schedule</term>
<term>Female</term>
<term>Histone Deacetylase Inhibitors</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Polymerase Chain Reaction</term>
</keywords>
</textClass>
<langUsage><language ident="en">en</language>
</langUsage>
</profileDesc>
</teiHeader>
<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. © 2007 Movement Disorder Society</div>
</front>
</TEI>
</ISTEX>
</double>
</record>

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	Movement Disorders (revue)
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Movement Disorders (revue)

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

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

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