Experimental gene therapy reverses fragile X symptoms in mice

An experimental gene therapy reversed several symptoms of fragile X syndrome in mice, according to a study published in Gene Therapy. The research was led by investigators at Cincinnati Children's and collaborators at Forge Biologics. The study tested adeno-associated viral vectors carrying the human FMR1 gene, which is silenced in fragile X syndrome. The approach produced the FMRP protein in key brain regions and improved multiple traits in Fmr1 knockout mice. Improvements included reduced susceptibility to audiogenic seizures, improvements in sensory hyperactivity and repetitive digging behavior, and normalization of elevated low-gamma EEG power. Christina Gross, PhD, co-corresponding author and researcher in the Division of Neurology at Cincinnati Children's, said the findings show that restoring FMRP can improve several fragile X-related traits in a model designed with clinical translation in mind. Ernest Pedapati, MD, MS, co-corresponding author, said re-expression of FMRP in mice at ages equivalent to 4-6 and 15-30 years in humans has the potential to rescue sensory hypersensitivity, stereotypic behavior, and excessive EEG gamma power. The study notes the approach has not been tested in people and more research is needed to evaluate safety, durability, dosing, immune responses and timing.