Trial of fenobam, an mGluR5 antagonist, in adults with Fragile X Syndrome

2009

Background: Recent advances in the study of the Fragile X knockout mouse model have demonstrated enhanced activity of the metabolic glutamate receptor 5 (mGluR5) pathway. The use of mGluR5 antagonists has rescued behavioural, cognitive and dendritic structural abnormalities in the knockout mouse. An initial phase II trial in adults with FXS was approved by the FDA. Method: We have completed this initial trial of fenobam (50 mg to 150 mg/dose) in twelve adults with FXS (mean age 23.9 (SD 5.4; range 18.7-30.7 years) seen either at UC Davis MIND Institute or at RUSH, University in Chicago, to assess safety, side-effects, and metabolism after a single dose. Results: Outcome measures included prepulse inhibition (PPI) and a continuous performance task (CPT). All patients tolerated this single dose without significant side-effects. The metabolism of fenobam in patients with FXS is similar to controls and peaks at approximately 180 minutes after oral dose. Fifty percent of the patients had a 20% or more improvement in PPI that is significantly different from test-retest changes in PPI previously reported in individuals with FXS (p = 0.03). This effect was more pronounced in males. The majority of patients scored at ceiling on the CPT so it was not a helpful measure to assess medication benefits. Conclusion: This work documents the safety and aspects of the metabolism of fenobam in patients with FXS and will facilitate further expansion of fenobam trials in patients with FXS. Although fenobam is a targeted treatment for FXS, subgroups of autism may also benefit from fenobam treatment.

Peer-reviewed publications in scholarly journals Published/In Press

Professionals

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