FXS is the most common inherited cause of intellectual disability (mental retardation) and the most prevalent known cause of autism. FXS is caused by the mutation of a single gene known as FMR1. FMR1 codes for a protein called fragile X mental retardation protein (FMRP) that is necessary for normal brain development. Without FMRP, patients exhibit several changes in their brains that underlie the cognitive and behavioral deficits associated with FXS. These changes include: alterations of neuronal morphology and an imbalance between excitatory and inhibitory neurotransmission in the brain. In addition, changes in localized protein synthesis have been observed in mouse models of FXS.
In the paper entitled "Postnatal pharmacological activation of the GABA-B receptor has potential to be disease-modifying in fragile X syndrome," the researchers tested whether STX209 was effective in reversing the hallmark changes in the brains of mice lacking the Fmr1 gene. In vitro application of STX209 to the hippocampus of mice lacking Fmr1 reduced levels of localized protein synthesis to that of normal mice. Additionally, this treatment reduced a known functional consequence of increased protein synthesis, AMPA receptor internalization, to levels found in normal mice. Furthermore, in vivo administration of STX209 corrected alterations in neuronal morphology specific to Fmr1-deficient mice and FXS patients, but STX209 did not alter neuronal morphology in normal mice and STX209 also reduced protein translation in mice lacking Fmr1, but not in normal mice. Of note, the magnitu
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