Metformin as targeted treatment in fragile X syndrome
Open accessAbstract
BACKGROUND: Individuals with fragile X syndrome (FXS) have both behavioral and medical comorbidities and the latter include obesity in approximately 30% and the Prader-Willi Phenotype (PWP) characterized by severe hyperphagia and morbid obesity in less than 10%. Metformin is a drug used in individuals with type 2 diabetes, obesity or impaired glucose tolerance and it has a strong safety profile in children and adults. Recently published studies in the Drosophila model and the knock out mouse model of FXS treated with metformin demonstrate the rescue of multiple phenotypes of FXS. MATERIALS AND METHODS: We present 7 cases of individuals with FXS who have been treated with metformin clinically. One case with type 2 diabetes, 3 cases with the PWP, 2 adults with obesity and/or behavioral problems and, a young child with FXS. These individuals were clinically treated with metformin and monitored for behavioral changes with the Aberrant Behavior Checklist and metabolic changes with a fasting glucose and HgbA1c. RESULTS: We found consistent improvements in irritability, social responsiveness, hyperactivity, and social avoidance, in addition to comments from the family regarding improvements in language and conversational skills. No significant side-effects were noted and most patients with obesity lost weight. CONCLUSION: We recommend a controlled trial of metformin in those with FXS. Metformin appears to be an effective treatment of obesity including those with the PWP in FXS. Our study suggests that metformin may also be a targeted treatment for improving behavior and language in children and adults with FXS.
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Studies of metformin were first carried out in patients with FXS who demonstrated obesity, often with the Prader-Willi-phenotype of FXS.
“Therefore, studies of metformin were first carried out in patients with FXS who demonstrated obesity, often with the Prader-Willi-phenotype of FXS [109].”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [109]
Parents stated that they saw improvement in expressive language abilities in conversation in patients with FXS treated with metformin.
“Parents also stated that they saw improvement in the expressive language abilities in conversation.”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [109]
In a handful of patients with FXS treated clinically with metformin between ages 4 and 60, there was improvement in overeating and on the ABC subscales of irritability, aggression, and social avoidance.
“In a handful of patients with FXS treated clinically with metformin between the ages of 4 and 60 years old, there was improvement in overeating but also on the ABC subscales of irritability, aggression, and social avoidance [109].”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [109]
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“Metformin, targeting ERK1/2 downstream of IGF-1, likewise appeared beneficial in an open-label study and increased GABAergic inhibition (Dy et al., 2018; Proteau-Lemieux et al., 2021).”
Background
- Authors
- Dy, A. B. C., Tassone, F., Eldeeb, M., Salcedo‐Arellano, M. J., Tartaglia, N., & Hagerman, R.
- Affiliations
- Ateneo de Manila University (PH)
- University of California Davis Medical Center (US)
- University of Colorado Anschutz (US)
- Corresponding author
- Hagerman, R.
- Venue
- Clinical Genetics
- Publisher
- Wiley
- Published
- 2017-09-25
- Volume
- 93
- Issue
- 2
- Pages
- 216-222
- ISSN
- 0009-9163 (ISSN-L)
- 1399-0004
- PMC
- PMC6944702
- OpenAlex
- W2610023271
- Cited by
- 124
- References
- 24
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 15 · 2023: 13 · 2022: 17 · 2021: 13 · 2020: 19 · 2019: 14 · 2018: 6 · 2017: 3
- FWCI
- 7.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- United States National Institute of Child Health and Human Development (R01 HD036071, U54 HD079125)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
- Keywords
- fragile X syndrome, metformin, obesity, hyperphagia, type 2 diabetes, behavioral comorbidities, irritability, social responsiveness, weight loss, targeted therapy
- MeSH terms
- Adult, Animals, Mental Disorders, Child, Child, Preschool, Diabetes Mellitus, Type 2, Female, Fragile X Syndrome, Glycated Hemoglobin, Humans, Male, Metformin, Middle Aged, Obesity, Prader-Willi Syndrome, Treatment Outcome, Glucose Intolerance, Young Adult
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