Emerging pharmacological therapies in fragile X syndrome and autism.

Abstract

Research on the pathophysiology of syndromic autism spectrum disorder (ASD) has contributed to the uncovering of mechanisms in nonsyndromic ASD. The current review aims to compare recent progress in therapeutics development for ASD with those for fragile X syndrome (FXS), the most frequent monogenic form of ASD. Although candidates such as oxytocin, vasopressin, and cannabinoids are being tested as novel therapeutics, it remains difficult to focus on a specific molecular target of drug development for ASD core symptoms. As the pathophysiology of FXS has been well described as having a causal gene, fragile X mental retardation-1, development of therapeutic agents for FXS is focused on specific molecular targets, such as metabotropic glutamate receptor 5 and GABAB receptor. There is a large unmet medical need in ASD, a heterogeneous and clinically defined behavioral syndrome, owing to its high prevalence in the general population, lifelong cognitive and behavioral deficits, and no established treatment of ASD core symptoms, such as deficits in social communication and restrictive repetitive behaviors. The molecular pathogenesis of nonsyndromic ASD is largely undefined. Lessons from initial attempts at targeted treatment development in FXS, and new designs resulting from these lessons, will inform trials in nonsyndromic ASD for development of therapeutics for its core symptoms.