Metformin Reverses Some Autism Symptoms In Animal Model Interview with:
Ilse Gantois, PhD

Research Associate
Dr. Nahum Sonenberg’s laboratory
Department of Biochemistry
McGill University What is the background for this study? What are the main findings?

Response: Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by cognitive impairment and affects 1 in 4000 males and 1 in 6000 females. About 60% of persons with Fragile X also have autism spectrum disorder. FXS is caused by absence of Fragile X protein (FMRP), which results in hyperactivation of ERK (extracellular signal-regulated kinase) and mTORC1 (mechanistic target of rapamycin complex 1) signaling. We show that treatment with metformin, the most widely used FDA-approved antidiabetic drug, suppresses translation by inhibiting the ERK pathway, and alleviates a variety of behavioural deficits, including impaired social interaction and excessive grooming. In addition, metformin also reversed defects in dendritic spine morphogenesis and synaptic transmission. What should readers take away from your report?

Response: Our data show that metformin, the most widely used FDA-approved antidiabetic drug, corrects most phenotypic deficits in the adult FXS mouse model. These results, along with the published data from Dr. Hagerman’s group in patients, raise the possibility that this drug could be repurposed for the treatment of FXS in the clinic. What recommendations do you have for future research as a result of this study?

Response: We want to further study the mechanism of how metformin exactly works in the brain, what molecules metformin interacts with and what cellular functions are affected. Furthermore, we want to study if metformin is also able to reverse a variety of behavioural and morphological deficits in other mouse models of ASD. These findings may lead to beneficial effects of metformin for other types of autism. Is there anything else you would like to add?

Response: Our findings in the mouse model raise the possibility that the drug can be repurposed for the treatment of FXS in the clinic, and might also be beneficial for other types of autism. Thank you for your contribution to the community.


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. Metformin ameliorates core deficits in a mouse model of fragile X syndrome. Nature Medicine, 2017; DOI: 10.1038/nm.4335
Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on May 24, 2017 by Marie Benz MD FAAD