Fragile X syndrome (FXS) is the leading monogenic cause of autism spectrum disorders (ASD). Trinucleotide repeat expansions in FMR1 abolish FMRP expression, leading to hyperactivation of ERK and mTOR signaling upstream of mRNA translation. Here we show that metformin, the most widely used drug for type 2 diabetes, rescues core phenotypes in Fmr1-/y mice and selectively normalizes ERK signaling, eIF4E phosphorylation and the expression of MMP-9. Thus, metformin is a potential FXS therapeutic.
Bibliographical noteFunding Information:
This work is supported by the FRAXA Research Foundation, Brain Canada/FNC, a CIHR foundation grant (FDN-148423) and Brain & Behavior Research Foundation grants (24365) to N.S.; a Wellcome Trust/Royal Society Sir Henry Dale grant (107687/Z/15/Z) to C.G.G.; the Canada Research Chair Program (950-231066) to J.-C.L.; and a Brain Canada/NeuroDevNet Postdoctoral Training Award to J.P.