Preclinical Testing of Drug Mimics of the Ketogenic Diet in Fragile X Mice

The ketogenic diet is highly effective at attenuating seizures in refractory epilepsy, and accumulating evidence in the literature suggests that it may be beneficial in autism. To our knowledge, no one has studied the ketogenic diet in any fragile X syndrome (FXS) model. FXS is the leading known genetic cause of autism. Herein, we tested the effects of chronic ketogenic diet treatment on seizures, body weight, ketone and glucose levels, diurnal activity levels, learning and memory, and anxiety behaviors in Fmr1KO and littermate control mice as a function of age. The ketogenic diet selectively attenuates seizures in male but not female Fmr1KO mice and differentially affects weight gain and diurnal activity levels dependent on Fmr1 genotype, sex and age.