TARGETING DOPAMINERGIC DYSFUNCTION IN FRAGILE X SYNDROME

Fragile X Syndrome (FXS) is the most common genetic cause of autism spectrum disorder (ASD), resulting from a mutation in the FMR1 gene that leads to the absence of Fragile X Messenger Ribonucleoprotein (FMRP) and dysregulated protein synthesis. Individuals with FXS frequently display autism-like behaviors, including social deficits, communication impairments, and repetitive behaviors, which have been linked to dopaminergic system dysfunction, particularly in the striatum. This study investigated the potential of a novel dopamine stabilizer with antipsychotic properties, to modulate dopamine regulation and improve behavioral outcomes in a mouse model of FXS. Behavioral assessments were conducted in Fmr1 knockout and wild-type mice to evaluate the effects of (-)-OSU6162 on motor activity, social interaction, and repetitive behaviors. Striatal dopamine levels were also measured to explore the neurochemical effects of the treatment. The results demonstrated that (-)-OSU6162 attenuated dopamine dysregulation in the striatum of Fmr1 knockout mice and was associated with reduced hyperactivity and repetitive behaviors, and improved social interaction. These findings suggest a promising therapeutic approach for addressing core behavioral symptoms in FXS by stabilizing dopaminergic signaling.