title: Molecular medicine of fragile X syndrome: based on known molecular mechanisms.
abstract: BACKGROUND
  Extensive research on fragile X mental retardation gene knockout mice and mutant Drosophila models has largely expanded our knowledge on mechanism-based treatment of fragile X syndrome (FXS). In light of these findings, several clinical trials are now underway for therapeutic translation to humans.
  
  
  METHODS
  Electronic literature searches were conducted using the PubMed database and ClinicalTrials.gov. The search terms included "fragile X syndrome", "FXS and medication", "FXS and therapeutics" and "FXS and treatment". Based on the publications identified in this search, we reviewed the neuroanatomical abnormalities in FXS patients and the potential pathogenic mechanisms to monitor the progress of FXS research, from basic studies to clinical trials.
  
  
  RESULTS
  The pathological mechanisms of FXS were categorized on the basis of neuroanatomy, synaptic structure, synaptic transmission and fragile X mental retardation protein (FMRP) loss of function. The neuroanatomical abnormalities in FXS were described to motivate extensive research into the region-specific pathologies in the brain responsible for FXS behavioural manifestations. Mechanism-directed molecular medicines were classified according to their target pathological mechanisms, and the most recent progress in clinical trials was discussed.
  
  
  CONCLUSIONS
  Current mechanism-based studies and clinical trials have greatly contributed to the development of FXS pharmacological therapeutics. Research examining the extent to which these treatments provided a rescue effect or FMRP compensation for the developmental impairments in FXS patients may help to improve the efficacy of treatments.
authors.affiliation: State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, China.
authors.forename: Shi-Yu
authors.initials: SY
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, China.
authors.forename: Ling-Qian
authors.initials: LQ
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, China. duanranhui@sklmg.edu.cn.
authors.forename: Ran-Hui
authors.initials: RH
authors.lastname: Duan
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D002648:Child; D005600:Fragile X Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D062346:Molecular Medicine
keywords: clinical trial; fragile X syndrome; mechanism-based; treatment