Metformin for treatment of fragile X syndrome and other neurological disorders
Open accessAbstract
Fragile X syndrome (FXS) is the most frequent inherited form of intellectual disability and autism spectrum disorder. Loss of the fragile X mental retardation protein, FMRP, engenders molecular, behavioral, and cognitive deficits in FXS patients. Experiments using different animal models advanced our knowledge of the pathophysiology of FXS and led to the discovery of many targets for drug treatments. In this review, we discuss the potential of metformin, an antidiabetic drug approved by the US Food and Drug Administration, to correct core symptoms of FXS and other neurological disorders in humans. We summarize its mechanisms of action in different animal and cellular models and human diseases.
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Animal studies in FXS have demonstrated a hyperactive insulin receptor and up-regulation of mTORC1 and MAPK/ERK signaling pathways, as well as elevation of MMP-9 levels in the absence of FMRP.
“Animal studies in FXS have demonstrated a hyperactive insulin receptor and up-regulation of the mammalian target of rapamycin complex 1 (mTORC1) and mitogen-activated protein kinase/extracellular signal-related kinases (MAPK/ERK) signaling pathways, as well as elevation of MMP-9 levels in the absence of FMRP, the protein produced by the FMR1 gene [106–108].”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [106]
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An Update on Psychopharmacological Treatment of Autism Spectrum Disorder
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Self-citationMetformin treatment in young children with fragile X syndrome
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- Authors
- Gantois, I., Popic, J., Khoutorsky, A., & Sonenberg, N.
- Affiliations
- Institut du cancer Rosalind & Morris Goodman (CA)
- Department of Biochemistry, McGill University, Montréal H3A 2T5, Québec, Canada;, ,
- McGill University (CA)
- Corresponding author
- Gantois, Ilse
- Venue
- Annual Review of Medicine
- Publisher
- Annual Reviews
- Published
- 2019-01-27
- Volume
- 70
- Issue
- 1
- Pages
- 167-181
- ISSN
- 0066-4219 (ISSN-L)
- 1545-326X
- OpenAlex
- W2898096243
- Cited by
- 87
- References
- 99
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 12 · 2023: 8 · 2022: 10 · 2021: 15 · 2020: 17 · 2019: 10
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annual Review of Medicine (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@McGill (McGill) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Keywords
- metformin, fragile X syndrome, FMRP, intellectual disability, autism spectrum disorder, drug repurposing, antidiabetic drugs, neurological disorders, animal models, mechanism of action
- MeSH terms
- Animals, Autistic Disorder, Disease Models, Animal, Fragile X Syndrome, Humans, Metformin, Nervous System Diseases, Parkinson Disease, Prognosis, Treatment Outcome, Mice, Fragile X Messenger Ribonucleoprotein 1, TOR Serine-Threonine Kinases
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