UCLA Health researchers have identified a potential drug target for treating fragile X syndrome (FXS), the most common genetic cause of intellectual disability and autism that affects roughly one in 2,000 boys. Fragile X syndrome is caused by a mutation in a single gene, FMR1, that results in the loss of a protein critical for normal brain development and function. Headed by Carlos Portera-Cailliau, MD, PhD, professor of neurology at UCLA and member of the UCLA Brain Research Institute, the researchers, the team’s work in genetically engineered mice lacking the Fmr1 gene identified the synaptic protein EPAC2 as a potential therapeutic target for fragile X syndrome. Their study showed that blocking EPAC2 in the fragile X mouse model restored abnormal patterns of brain activity and improved several FXS-associated behavioral symptoms. Pertera-Cailliau is senior and corresponding author of the researchers published paper in Neuron, titled “Translatome profiling reveals opposing alterations in inhibitory and excitatory neurons of fragile X mice and identifies EPAC2 as a therapeutic target.” Fragile X syndrome is a prototypical neurodevelopmental disorder (NDD) characterized by intellectual disability, social anxiety, atypical sensory processing characterized heightened sensitivity to sensory input such as sound and touch, and a higher risk of seizures. Many also meet the criteria for an autism spectrum disorder diagnosis. “Symptoms of fragile X syndrome (FXS), the leading monogenic cause of intellectual disability and autism, are thought to arise from an excitation/inhibition (E/I) imbalance,” the authors stated. FXS is caused by mutations in the FMR1 gene, resulting in near…
