Clinical Trials and Cyclic AMP in Fragile X Syndrome: A Life Journey

Fragile X syndrome (FXS) was thought to be a model neurodevelopmental disorder for the translation of mechanism-targeted treatments from basic neuroscience and animal models to patients. Thus far, however, clinical trials of these approaches have failed. More recent refinements of trial designs and outcome measures have led to a successful phase II trial that targets abnormal cAMP regulation in FXS.

In this lecture, Elizabeth Berry-Kravis will focus on early findings of a cAMP production deficit in cells from FXS, FMR1 gene discovery, understanding of FMRP function and identification of downstream neural deficits. Learnings from resultant targeted treatment trials of disease-directed agents in FXS, which did not meet with success, and outcome measure refinement have been applied to more recent trial designs. The application of such advances has produced a successful outcome in the first trial targeting the cAMP deficit in FXS.

Berry-Kravis established the Fragile X Clinic and Research Program at Rush University Medical Center in 1992, which now provides care to more than 700 patients with FXS. She researches FXS and other neurogenetic diseases, including outcome measures, biomarkers, natural history studies and clinical trials in FXS, PMS, NPC, Angelman syndrome, Rett syndrome, and Down syndrome. She has led the translational effort to develop new models for targeted treatment for FXS.