Fragile X Syndrome and Targeted Treatment Trials ; Results Probl Cell Differ

Work in recent years has revealed an abundance of possible new treatment targets for fragile X syndrome (FXS). The use of animal models, including the fragile X knockout mouse which manifests a phenotype very similar to FXS in humans, has resulted in great strides in this direction of research. The lack of Fragile X Mental Retardation Protein (FMRP) in FXS causes dysregulation and usually overexpression of a number of its target genes, which can cause imbalances of neurotransmission and deficits in synaptic plasticity. The use of metabotropic glutamate receptor (mGluR) blockers and gamma amino-butyric acid (GABA) agonists have been shown to be efficacious in reversing cellular and behavioral phenotypes, and restoring proper brain connectivity in the mouse and fly models. Proposed new pharmacological treatments and educational interventions are discussed in this chapter. In combination, these various targeted treatments show promising preliminary results in mitigating or even reversing the neurobiological abnormalities caused by loss of FMRP, with possible translational applications to other neurodevelopmental disorders including autism. ; 90DD05969/DD/NCBDD CDC HHS/United States ; AG032115/AG/NIA NIH HHS/United States ; AG032119/AG/NIA NIH HHS/United States ; DA024854/DA/NIDA NIH HHS/United States ; DE019583/DE/NIDCR NIH HHS/United States ; HD02274/HD/NICHD NIH HHS/United States ; HD036071/HD/NICHD NIH HHS/United States ; MH082042/MH/NIMH NIH HHS/United States ; P30 HD002274/HD/NICHD NIH HHS/United States ; R01 HD036071/HD/NICHD NIH HHS/United States ; R01 MH082042/MH/NIMH NIH HHS/United States ; RL1 AG032115/AG/NIA NIH HHS/United States ; RL1 AG032119/AG/NIA NIH HHS/United States ; TL1 DA024854/DA/NIDA NIH HHS/United States ; UL1 DE019583/DE/NIDCR NIH HHS/United States ; UL1 RR024146/RR/NCRR NIH HHS/United States ; UL1RR024146/RR/NCRR NIH HHS/United States ; 2014-07-29T00:00:00Z ; 22009360 ; PMC4114775