With a $50,000 grant from FRAXA Research Foundation, Dr. Artuela Çaku and Dr. Francois Corbin completed an open label clinical trial of metformin for children and adults with Fragile X syndrome. Published results showed no increase in adverse events (metformin was well tolerated). Transcranial Magnetic Stimulation (TMS) data showed an increase in corticospinal inhibition mediated by GABAA and GABAB mechanisms.
Artuela Çaku MD
Jean-François Lepage, PhD
University of Sherbrooke
2018-2019 FRAXA Clinical Trial
$50,000 over 2 years
Metformin is the most commonly prescribed drug for type 2 diabetes, to control high blood sugar. With FRAXA funding, several investigators including Nahum Sonenberg, Sean McBride and Tom Jongens have shown that metformin can also correct many signs of Fragile X in mouse and fly models. In these animal models, metformin normalizes several aspects of neuron-to-neuron communication which are impaired in Fragile X, including ERK signaling, EIF4E phosphorylation, and expression of MMP9.
While a growing number of families are trying metformin and reporting mixed results, metformin has not yet been systematically studied in patients with Fragile X syndrome. This open-label trial is designed to better understand the safety and efficacy of this medicine on behavior and cognition, and to find the best dosages for children and adults.
What's Involved in this Study?
15 individuals with Fragile X syndrome, aged from 17 to 44, took metformin 250mg twice a day for the first week, followed by metformin 500mg twice a day for the next 8 weeks. The primary outcome measures were: (1) the incidence of adverse events; (2) the decrease in IGF-1 levels; and (3) the global score of the Aberrant Behavior Checklist-Community, Fragile X. The secondary outcomes were: (1) the Test of Attentional Performance for children (KiTAP); and (2) the Transcranial Magnetic Stimulation (TMS) parameters measuring cortical excitability.
This study demonstrates the safety of metformin in normoglycemic patients with FXS. Researchers did not find changes on either primary outcome measure. TMS data showed an increase in corticospinal inhibition mediated by GABAA and GABAB mechanisms. Thus the results suggest that metformin might modify GABA-mediated inhibition, a hallmark of FXS pathophysiology.