Metformin ameliorates core deficits in a mouse model of fragile X syndrome

• DOI: 10.1038/nm.4335
• Publication Date: 2017-05-15T15:01:06Z
• Authors: Ilse Gantois; Arkady Khoutorsky; Jelena Popic; Argel Aguilar-Valles; Erika Freemantle; Ruifeng Cao; Vijendra Sharma; Tine Pooters; Anmol Nagpal; Agnieszka Skalecka; Vinh T Truong; Shane Wiebe; Isabelle A Groves; Seyed Mehdi Jafar...; Clément Chapat; Elizabeth A McCul...; Karine Gamache; Karim Nader; Jean-Claude Lacaille; Christos G Gkogkas; Nahum Sonenberg
• Keywords: Male; Mice, Knockout; 0303 health sciences; Behavior, Animal; MAP Kinase Signaling System; Biochemistry; Metformin; 3. Good health; Disease Models, Animal; Fragile X Mental Retardation Protein; Mice; 03 medical and health sciences; Eukaryotic Initiation Factor-4E; Matrix Metalloproteinase 9; Fragile X Syndrome; Animals; Hypoglycemic Agents; RNA, Messenger; Phosphorylation; Social Behavior; Trinucleotide Repeat Expansion

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.