Therapeutic approaches for the future treatment of Fragile X

•FXS is the most common inherited cause of intellectual disability.•Fragile X is a common single-gene cause of autism spectrum disorder.•It is caused by loss of expression of FMRP that negatively regulates protein synthesis.•This review highlights the most recent advances in the field of fragile X research.

Fragile X syndrome (FXS) is a common form of mental disability characterized by hypersensitivity to sensory stimuli, hyperactivity and severe cognitive impairment. FXS is caused by loss of the fragile X mental retardation 1 (FMR1) gene, whose fragile X mental retardation protein (FMRP) regulates mRNA translation downstream of synaptic activity to modulate changes in synaptic architecture, function and plasticity. FXS is one of the known causes of autism and there is no effective treatment that corrects the deficit in FMRP. However, new advances in the knowledge of the molecular pathophysiology of FXS have opened different strategies for the future development of effective drugs. Among the emerging targets are several protein kinases, neuronal calcium sensors, muscarinic receptors, potassium channels, endocannabinoid system, etc. Moreover, some small molecules such statins, antioxidants, glycogen synthase kinase 3 inhibitors among others have showed an improved in cognition and behavioral tests in FXS mouse model emerging as promising drug candidates for FXS pharmacological treatment in the next future.

Graphical abstractDownload full-size image