Improvement of Behavioral Effects of Fragile X Syndrome

Inhibition of mGluR5 receptor may improve fragile X syndrome attributes in some patients

MONDAY, Jan. 31 (HealthDay News) -- Evaluation of a selective metabotropic glutamate receptor 5 (mGluR5) inhibitor in treating fragile X Syndrome (FXS) indicates improvement in patients with a fully methylated fragile X mental retardation 1 (FMR1) gene, according to a study published in the Jan. 5 issue of Science Translational Medicine.

Sébastien Jacquemont, M.D., from Vaudois University in Lausanne, Switzerland, and colleagues examined whether AFQ056, a receptor subtype-selective inhibitor of mGluR5, improved the behavioral symptoms of patients with FXS. Thirty male patients, aged 18 to 35, were randomized in a double-blind, two-treatment, two-period crossover study and their behavioral outcome was assessed.

The investigators did not detect any significant effect of treatment on the Aberrant Behavior Checklist-Community Editing (ABC-C) score at day 19 or 20 of treatment. However, ABC-C scores for seven patients improved significantly after treatment with AFQ056 compared with placebo. Genetic analysis identified full FMR1 promoter methylation in these patients. Patients with partial methylation did not respond to AFQ056 treatment.

"We have shown that the selective inhibition of mGluR5 by AFQ056 can provide a significant effect on behavioral problems in a subpopulation of patients with FXS. If confirmed in future studies, these results suggest that AFQ056 may provide valuable improvement in behavioral symptoms of FXS and that this improvement is predicted by full methylation at the FMR1 promoter," the authors write.

Several of the study authors disclosed financial ties to pharmaceutical companies.

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