Challenges in Conducting Clinical Trials for Pharmacotherapies in Fragile X Syndrome: Lessons Learned

摘要

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and most common single gene cause of autism spectrum disorder (ASD). Even in the context of a single gene disorder like FXS, characteristic cognitive and behavioral heterogeneity creates challenges in conducting targeted pharmacotherapy trials. Neuroscientific advances have elucidated aspects of the underlying neurobi-ology in FXS and have guided targeted treatment development in the last decade. However, despite significant preclinical progress, recent clinical trials have failed to consistently demonstrate therapeutic efficacy based on behavioral outcome measures in patients with FXS. One potential explanation for these failures is that many behavioral measures are not capable of quantitively capturing clinically significant change in such short-term trials. Further, the use of parent and clinician report instruments as primary outcome measures creates additional challenges in clinical trials.