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

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 Jafarnejad; Clément Chapat; Elizabeth A. McCullagh; Karine Gamache; Karim Nader; Jean Claude Lacaille; Christos G. Gkogkas; Nahum Sonenberg

doi:10.1038/nm.4335

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

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 Jafarnejad, Clément Chapat, Elizabeth A. McCullagh, Karine Gamache, Karim Nader, Jean Claude Lacaille, Christos G. GkogkasNahum Sonenberg

Biomedical Sciences

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Abstract

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.

Original language	English (US)
Pages (from-to)	674-677
Number of pages	4
Journal	Nature Medicine
Volume	23
Issue number	6
DOIs	https://doi.org/10.1038/nm.4335
State	Published - Jun 1 2017

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© 2017 Nature America, Inc., part of Springer Nature. All rights reserved.

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Gantois, I., Khoutorsky, A., Popic, J., Aguilar-Valles, A., Freemantle, E., Cao, R., Sharma, V., Pooters, T., Nagpal, A., Skalecka, A., Truong, V. T., Wiebe, S., Groves, I. A., Jafarnejad, S. M., Chapat, C., McCullagh, E. A., Gamache, K., Nader, K., Lacaille, J. C., ... Sonenberg, N. (2017). Metformin ameliorates core deficits in a mouse model of fragile X syndrome. Nature Medicine, 23(6), 674-677. https://doi.org/10.1038/nm.4335

Gantois, I, Khoutorsky, A, Popic, J, Aguilar-Valles, A, Freemantle, E, Cao, R, Sharma, V, Pooters, T, Nagpal, A, Skalecka, A, Truong, VT, Wiebe, S, Groves, IA, Jafarnejad, SM, Chapat, C, McCullagh, EA, Gamache, K, Nader, K, Lacaille, JC, Gkogkas, CG & Sonenberg, N 2017, 'Metformin ameliorates core deficits in a mouse model of fragile X syndrome', Nature Medicine, vol. 23, no. 6, pp. 674-677. https://doi.org/10.1038/nm.4335

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

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