Advances in Understanding Disease Mechanisms and Translation to Therapeutics

The Fragile X and Autism-Related Disorders GRC is a premier, international scientific conference focused on advancing the frontiers of science through the presentation of cutting-edge and unpublished research, prioritizing time for discussion after each talk and fostering informal interactions among scientists of all career stages. The conference program includes a diverse range of speakers and discussion leaders from institutions and organizations worldwide, concentrating on the latest developments in the field. The conference is five days long and held in a remote location to increase the sense of camaraderie and create scientific communities, with lasting collaborations and friendships. In addition to premier talks, the conference has designated time for poster sessions from individuals of all career stages, and afternoon free time and communal meals allow for informal networking opportunities with leaders in the field.

Genetic syndromes with increased prevalence of autism spectrum disorder (ASD) and intellectual disability (ID) offer an opportunity to understand the brain pathophysiology that manifests as ASD; this knowledge can suggest potential targeted therapies. It is now clear that the genetics underlying ASD are complex; with at least several hundred genes conferring small amounts of risk. Studies utilizing genomic sequencing and found several rare variants in individuals with ASD. These studies suggest a high degree of convergence on particular cellular processes and biochemical pathways, suggesting there may be convergence of underlying mechanisms and potential therapeutic strategies. The study of monogenic or syndromic forms of ASD, has been a leading strategy to gain insight into the complex mechanisms of ASD. Fragile X Syndrome (FXS) is one of the most common inherited forms of ID and the leading single gene cause of ASD. Since the Fragile X gene (FMR1) was cloned in 1991, the field has used cellular assays and model organisms to elucidate the functions of the FMR1 protein (FMRP), the consequences of its loss and identify therapeutic targets for FXS and ASD. Other syndromic forms of ASD, such as tuberous sclerosis complex, Rett Syndrome, Angelman Syndrome and others, are being investigated using similar approaches. Recent technological advances in human stem-cell derived neurons, organoids, single cell sequencing, gene therapy and novel model organisms are setting the stage for transformative advances in therapeutic development for these neurodevelopmental disorders. This conference will bring together leading scientists and clinicians studying FXS, ASD and related neurodevelopmental disorders with the ultimate goal of identifying the mechanisms that underlie the heterogeneous symptomatology associated with these disorders and the best potential pathways for translating this knowledge into clinical trials.