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Showing papers by "Joanne M. Meyer published in 2011"

Journal Article•DOI•
Epigenetic Modification of the FMR1 Gene in Fragile X Syndrome Is Associated with Differential Response to the mGluR5 Antagonist AFQ056

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Sébastien Jacquemont1, Aurore Curie2, Vincent des Portes2, Maria Giulia Torrioli3, Elizabeth Berry-Kravis4, Randi J Hagerman5, Feliciano J. Ramos6, Kim Cornish7, Yunsheng He8, Charles Paulding8, Giovanni Neri3, Fei Chen9, Fei Chen1, Nouchine Hadjikhani10, Nouchine Hadjikhani9, Danielle Martinet1, Joanne M. Meyer8, Jacques S. Beckmann1, Karine Delange2, Amandine Brun2, Gérald Bussy2, Fabrizio Gasparini8, Talita Hilse8, Annette Floesser8, Janice Branson8, Graeme Bilbe8, Donald Johns8, Baltazar Gomez-Mancilla8 •
University Hospital of Lausanne1, University of Lyon2, Catholic University of the Sacred Heart3, Rush University Medical Center4, University of California, Davis5, University of Zaragoza6, Monash University7, Novartis8, École Polytechnique Fédérale de Lausanne9, Harvard University10
05 Jan 2011-Science Translational Medicine
TL;DR: An antagonist for the metabotropic glutamate receptor may improve symptoms in patients with fragile X syndrome whose FMR1 promoters are fully methylated, a sign that gene expression is completely silenced, and provides the basis for a larger study to test whether methylation can serve as a predictor of a positive antagonist response in a population of patients with Fragile X syndrome.
Abstract: 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. ThismutationisassociatedwithhypermethylationattheFMR1promoterandresultanttranscriptionalsilencing.FMR1 silencinghasmanyconsequences,includingup-regulationofmetabotropicglutamatereceptor5(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.

611 citations

Patent•
Predictive Markers Useful in the Treatment of Fragile X Syndrome (FXS)

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Baltazar Gomez-Mancilla, Yunsheng He, Donald Johns, Joanne M. Meyer, Charles Paulding 
28 Apr 2011
TL;DR: In this article, the use of biomarkers to determine responsiveness of an individual with Fragile X Syndrome (FXS) to treatment with an mGluR5 antagonist was proposed.
Abstract: The invention is directed to the use of biomarkers to determine responsiveness of an individual with Fragile X Syndrome (FXS) to treatment with an mGluR5 antagonist.

38 citations

Journal Article•
Antagonism of mGluR5 in Fragile X: A Randomized, Placebo-Controlled, Proof-of-Concept Study of AFQ056, a Novel, Sub-Type Selective mGluR5 Antagonist

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Baltazar Gomez-Mancilla, Sébastien Jacquemont, Aurore Curie, Vincent des Portes, Maria Giulia Torrioli, Elizabeth Berry-Kravis, Randi J Hagerman, Feliciano J. Ramos, Kim Cornish, Yunsheng He, Charles Paulding, Giovanni Neri, Fei Chen, Nouchine Hadjikhani, Danielle Martinet, Joanne M. Meyer, Jacques S. Beckmann, Karine Delange, Amandine Brun, Gérald Bussy, Fabrizio Gasparini, Talita Hilse, Annette Floesser, Janice Branson, Graeme Bilbe, Donald Johns 
01 Jan 2011-Current Neuropharmacology
TL;DR: This poster presents a probabilistic reconstruction of the response of the immune system to repeated exposure to EPFL-conf-178514 high-energy particles and shows clear patterns of decline in the number of immune-inflammatory responses.
Abstract: Reference EPFL-CONF-178514View record in Web of Science Record created on 2012-06-25, modified on 2016-08-09

1 citations