Rare disorders (RDs) collectively affect a substantial proportion of the population, yet most lack clinically approved, mechanistically targeted therapies. Fragile X syndrome (FXS), the most common inherited cause of intellectual disability and a major genetic contributor to autism spectrum disorder, exemplifies this gap. Despite more than 3 decades of preclinical research and numerous pharmacologic clinical trials informed by disease mechanisms, no targeted therapy for FXS has received regulatory approval. This scoping review aims to evaluate the design characteristics, outcome measures, and reported effect sizes of pharmacologic clinical trials in FXS to highlight methodological limitations that may have hindered the accurate assessment of therapeutic efficacy in FXS and to inform future trials in RDs.
Steenbergen et al. (Tue,) studied this question.