Source:http://linkedlifedata.com/resource/pubmed/id/21209411
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
64
|
| pubmed:dateCreated |
2011-1-6
|
| pubmed:databankReference | |
| pubmed:abstractText |
Fragile X syndrome (FXS) is an X-linked condition associated with intellectual disability and behavioral problems. It is caused by expansion of a CGG repeat in the 5' untranslated region of the fragile X mental retardation 1 (FMR1) gene. This mutation is associated with hypermethylation at the FMR1 promoter and resultant transcriptional silencing. FMR1 silencing has many consequences, including up-regulation of metabotropic glutamate receptor 5 (mGluR5)-mediated signaling. mGluR5 receptor antagonists have shown promise in preclinical FXS models and in one small open-label study of FXS. We examined whether a receptor subtype-selective inhibitor of mGluR5, AFQ056, improves the behavioral symptoms of FXS in a randomized, double-blind, two-treatment, two-period, crossover study of 30 male FXS patients aged 18 to 35 years. We detected no significant effects of treatment on the primary outcome measure, the Aberrant Behavior Checklist-Community Edition (ABC-C) score, at day 19 or 20 of treatment. In an exploratory analysis, however, seven patients with full FMR1 promoter methylation and no detectable FMR1 messenger RNA improved, as measured with the ABC-C, significantly more after AFQ056 treatment than with placebo (P < 0.001). We detected no response in 18 patients with partial promoter methylation. Twenty-four patients experienced an adverse event, which was mostly mild to moderately severe fatigue or headache. If confirmed in larger and longer-term studies, these results suggest that blockade of the mGluR5 receptor in patients with full methylation at the FMR1 promoter may show improvement in the behavioral attributes of FXS.
|
| pubmed:commentsCorrections | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/FMR1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fragile X Mental Retardation Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Metabotropic Glutamate,
http://linkedlifedata.com/resource/pubmed/chemical/metabotropic glutamate receptor 5
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
1946-6242
|
| pubmed:author |
pubmed-author:BeckmannJacques SJS,
pubmed-author:Berry-KravisElizabethE,
pubmed-author:BilbeGraemeG,
pubmed-author:BransonJaniceJ,
pubmed-author:BrunAmandineA,
pubmed-author:BussyGeraldG,
pubmed-author:ChenFeiF,
pubmed-author:CornishKimK,
pubmed-author:CurieAuroreA,
pubmed-author:DelangeKarineK,
pubmed-author:FloesserAnnetteA,
pubmed-author:GaspariniFabrizioF,
pubmed-author:Gomez-MancillaBaltazarB,
pubmed-author:HadjikhaniNouchineN,
pubmed-author:HagermanRandi JRJ,
pubmed-author:HeYunshengY,
pubmed-author:HilseTalitaT,
pubmed-author:JacquemontSébastienS,
pubmed-author:JohnsDonaldD,
pubmed-author:MartinetDanielleD,
pubmed-author:MeyerJoanneJ,
pubmed-author:NeriGiovanniG,
pubmed-author:PauldingCharlesC,
pubmed-author:RamosFeliciano JFJ,
pubmed-author:TorrioliMaria GiuliaMG,
pubmed-author:des PortesVincentV
|
| pubmed:issnType |
Electronic
|
| pubmed:day |
5
|
| pubmed:volume |
3
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
64ra1
|
| pubmed:dateRevised |
2011-6-21
|
| pubmed:meshHeading |
pubmed-meshheading:21209411-Adult,
pubmed-meshheading:21209411-DNA Methylation,
pubmed-meshheading:21209411-Epigenesis, Genetic,
pubmed-meshheading:21209411-Fragile X Mental Retardation Protein,
pubmed-meshheading:21209411-Fragile X Syndrome,
pubmed-meshheading:21209411-Humans,
pubmed-meshheading:21209411-Male,
pubmed-meshheading:21209411-Middle Aged,
pubmed-meshheading:21209411-Promoter Regions, Genetic,
pubmed-meshheading:21209411-Receptors, Metabotropic Glutamate,
pubmed-meshheading:21209411-Young Adult
|
| pubmed:year |
2011
|
| pubmed:articleTitle |
Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056.
|
| pubmed:affiliation |
Service de Génétique Médicale, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland.
|
| pubmed:publicationType |
Journal Article,
Randomized Controlled Trial,
Research Support, Non-U.S. Gov't
|