Treatment with metformin, a common diabetes medicine, can help to improve language skills and behavior in young children with fragile X syndrome, a review study of nine patients reports.
Two clinical trials in children and adults with this syndrome are underway to better characterize metformin’s effects and safety, the study’s researchers noted. Both are recruiting patients at their respective sites.
Their work, “Metformin treatment in young children with fragile X syndrome,” was published in the journal Molecular Genetics & Genomic Medicine.
Metformin was first approved by the U.S. Food and Drug Administration for its ability to lower sugar levels in the blood of people with type 2 diabetes. It now is used in the U.S. to treat diabetes in adults and children, ages 10 and older.
Metformin is also being evaluated as a possible treatment of obesity and overeating.
Given its demonstrated safety in people and the cognitive and behavioral benefits seen in animal models of fragile X, University of California Davis Medical Center researchers explored its potential fragile X patients. The animal studies found metformin able to improve communication between brain cells, which is impaired in fragile X, and to ease such disease features as social deficits, seizures, and macroorchidism (enlarged testes) in a mouse model.
The researchers reviewed the clinical records of nine fragile X children (ages 2 to 7) who were treated with metformin off-label at their center. Doses were established and adjusted individually for each child, ranging from 25 mg once daily to 500 mg twice daily.
Their parents were asked to assess behavioral changes using the Aberrant Behavior Checklist‐Community (ABC‐C), a 58-item global list established to determine treatment effects in individuals with intellectual disability.
ABC-C data analysis showed statistically significant improvements in two of the six evaluated factors, lethargy (lack of energy and enthusiasm) and stereotypy (persistently repeating a certain action). Clinical data also reported improvements in receptive and expressive language after metformin treatment.
“The results of this preliminary clinical treatment of children with FXS 2–7 years old indicate the potential of metformin as a targeted treatment for young patients with FXS as data suggests language and cognitive benefits with no regression,” the researchers wrote.
But given the small size of this patient group, “no definitive conclusions can be drawn,” they added.
A controlled clinical trial is underway at the UC Davis MIND Institute (NCT03479476) to assess metformin in 60 people with fragile X syndrome, ages 6 to 25. Changes in language skills in treated patients compared to placebo is the main goal of this four-month trial, which is currently enrolling at its sole site.
A separate and open-label study (NCT03722290) in Canada is also now enrolling 20 fragile X patients, ages 10 to 40, to test metformin’s safety and impact on behavior (primary endpoints). All in this Quebec single-site study will be treated with metformin at 500 mg twice daily for eight weeks, after an initial week at 250 mg twice a day.