865. Metformin as a treatment of Fragile X and Phelan McDermid syndromes

Abstract

Abstract Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by core symptoms of persistent deficits in social communication and interaction, and repetitive behavior. Worldwide prevalence ranges between 1-2 %, with an incidence rate 4 times higher in males than females. Unfortunately, about 40% of children with ASD do not respond to standard behavioral and medical treatments. Aims & Objectives For the moment we are focusing on mouse models of Fragile X syndrome (FXS) and Phelan McDermid Syndrome (PMS), in both males and females. These 2 neurodevelopmental disorders have a very high incidence of ASD. Method We are studying the therapeutic effects of metformin, an FDA approved drug, for treating symptoms associated with ASD at a behavioral level. In addition, ERK/MAPK and mTOR pathways, involved in controlling mRNA translation, are overactivated in several brain areas of FXS and PMS mouse models. Results Metformin treatment, an inhibitor of these pathways, showed high efficacy in correcting pathway signaling and behavior in fragile X syndrome (FXS) fly and mouse models, and in male and female mouse models of PMS. Discussion & Conclusions Our work broadens the understanding of the effects of metformin on ASD and potentially supports the implementation of clinical strategies to alleviate symptoms associated with these neurological disorders in both sexes.