Fragile X targeted pharmacotherapy: Lessons learned and future directions

Craig A. Erickson, Matthew H. Davenport, Tori L. Schaefer, Logan K. Wink, Ernest V. Pedapati, John A. Sweeney, Sarah E. Fitzpatrick, W. Ted Brown, Dejan Budimirovic, Randi J. Hagerman, David Hessl, Walter E. Kaufmann, Elizabeth Berry-Kravis

Research output: Contribution to journalReview articlepeer-review

80 Scopus citations


Our understanding of fragile X syndrome (FXS) pathophysiology continues to improve and numerous potential drug targets have been identified. Yet, current prescribing practices are only symptom-based in order to manage difficult behaviors, as no drug to date is approved for the treatment of FXS. Drugs impacting a diversity of targets in the brain have been studied in recent FXS-specific clinical trials. While many drugs have focused on regulation of enhanced glutamatergic or deficient GABAergic neurotransmission, compounds studied have not been limited to these mechanisms. As a single-gene disorder, it was thought that FXS would have consistent drug targets that could be modulated with pharmacotherapy and lead to significant improvement. Unfortunately, despite promising results in FXS animal models, translational drug treatment development in FXS has largely failed. Future success in this field will depend on learning from past challenges to improve clinical trial design, choose appropriate outcome measures and age range choices, and find readily modulated drug targets. Even with many negative placebo-controlled study results, the field continues to move forward exploring both the new mechanistic drug approaches combined with ways to improve trial execution. This review summarizes the known phenotype and pathophysiology of FXS and past clinical trial rationale and results, and discusses current challenges facing the field and lessons from which to learn for future treatment development efforts.

Original languageEnglish (US)
Article number7
JournalJournal of neurodevelopmental disorders
Issue number1
StatePublished - Jun 12 2017


  • Drug development
  • Fragile X syndrome
  • Genetic disorder
  • Targeted treatments
  • Translational treatment

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cognitive Neuroscience


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