Transcending Barriers to Development of Targeted Treatments for Fragile X Syndrome

Despite extensive molecular, cellular and animal model data supporting disease pathway-targeted treatments in fragile X syndrome, initial clinical trials based on FDA precedents failed to show benefit for behavior in adult and adolescent humans with FXS. Rethinking of translational models and drug development strategies based on this experience has revealed gaps in understanding of optimal age of treatment, trial designs, need for better outcome measures and biomarkers that assay core aspects of the disease, and potential need to measure drug effects in the setting of a learning paradigm. Work has been done to address these issues and this process has informed design of more recent FXS trials, including novel trial designs in progress to show disease modification in terms of learning and functional improvements. Lessons learned in FXS trials and new designs developed for FXS can inform design of trials of targeted treatments for other single gene models of ASD, and for idiopathic ASD.