New Insights into Disease Mechanisms Leading to Improved Therapeutics for Neurodevelopmental Disorders

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and the most frequent single gene cause of autism, affecting approximately 1 in 4,000 males and 1 in 6,000 females. Autism spectrum disorders (ASD) occur in up to 2/3 of males and 1/3 of females with FXS. Since the Fragile X gene (FMR1) was cloned in 1991 a large field has grown with more than a hundred labs using techniques from biochemistry through genetics to model organisms to elucidate the functions of the FMR1 protein (FMRP). FMRP has traditionally been thought of as an RNA-binding protein that regulates the translation of a set of messages highly enriched for synaptic proteins in response to neural activity, causing synapses to strengthen or weaken with experience. More recently, other distinct functions of FMRP apart from RNA binding have been discovered which implicate this protein as a major regulator of synaptic plasticity via several mechanisms. A major goal of this meeting will be to explore new FXS disease mechanisms such as channelopathies, extracellular and retrograde signaling abnormalities, and glial dysfunction.

It has become clear that in addition to the clinical overlap between FXS and autism spectrum disorders (ASD), there is likely substantial overlap in the molecular pathology of the two disorders. Molecules aimed at targets in these shared pathways are now being developed and tested in academic and pharma laboratories. It is expected that many of these targeted treatments will have therapeutic overlap in subsets of individuals with ASD or neurodevelopmental disorders (NDD). This conference will bring together leading scientists and clinicians in the Fragile X, ASD, and NDD fields, particularly those working on forms of ASD/NDD with dysfunctions in molecular pathways that overlap those implicated in FXS.