Disease-Targeted Treatment Translation in Fragile X Syndrome as a Model for Neurodevelopmental Disorders.

Fragile X syndrome (FXS), the most common monogenic cause of intellectual disability and autism spectrum disorder, has been one of the first neurodevelopmental disorders in which molecular and neuronal mechanisms of disease were identified, leading to the concept of targeting the underlying disease to reverse symptoms. Translating findings in basic science and animal models to humans with FXS has proven difficult. These challenges have prompted the FXS field to organize to build interlocking projects and initiatives to improve consistency of supportive care, make clinical research accessible to families, generate collaborative research on natural history, outcome measures and biomarkers, and create clinical trial consortia and novel trial designs. This work has resulted in improved success in recent clinical trials, providing key steps toward regulatory approval of disease-targeted treatments for FXS. Progress in the FXS field has informed translation of transformative new disease-targeted therapies for other monogenic neurodevelopmental disorders.