A clinical trial of a drug to treat behavioural features of the genetic disorder fragile X syndrome has revealed a genetic signature that seems to predict which patients will respond to the treatment.

Fragile X syndrome results from excessive methylation of a regulatory section — called the promoter — of the FMR1 gene. This silences the gene and increases signalling in the pathway for the brain receptor mGluR5. The drug candidate, AFQ056, blocks mGluR5 activation.

Baltazar Gomez-Mancilla at the Novartis Institutes for Biomedical Research in Basel, Switzerland, and his group assessed the drug's effects on the behaviour of 30 men who had either a fully or partly methylated FMR1 promoter region. Seven with a fully methylated promoter showed behavioural improvements after 19–20 days, whereas the behaviour of those with only partial methylation did not differ significantly between drug and placebo treatments.

Sci. Transl. Med. 3, 64ra1 (2011)