Diabetes drug metformin shows promise in treating one form of autism

The diabetes drug metformin relieved behavioral symptoms in mouse models of fragile X syndrome.

Metformin has been helping patients with Type 2 diabetes control their blood sugar for more than two decades, but now researchers led by McGill University are investigating a new use for the drug: to treat fragile X syndrome, which causes some forms of autism.

Mouse models of fragile X show many of the telltale symptoms of the disease, including a lack of socialization. But within 10 days of being injected with metformin, their brain connections and behaviors were normal, according to a press release from the university. The research was published in the journal Nature Communications.

Fragile X is an inherited genetic disorder that causes excess protein production in the brain and improper connections between neurons. The disease impairs speech, behavior and social interactions and sometimes coexists with anxiety and seizures.

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The researchers observed that metformin restores molecular pathways that become disrupted by the defective gene, called the fragile X mental retardation 1 gene (FMR1), according to the release. They’re still trying to figure out exactly how the drug acts on those pathways, but their evidence suggests it may work in other forms of autism, too.

Autism is one of many medical conditions that scientists believe could be addressed with metformin. Observational studies have suggested that people with diabetes who take the drug have a decreased risk of cancer—a phenomenon that has set several scientific teams off on a mission to find out whether metformin might have antitumor effects. Last year, scientists at the University of California in San Diego published research suggesting that metformin fortifies epithelial cells, creating a barrier against cancer-causing agents.

The Albert Einstein College of Medicine in New York is using metformin in a trial among patients suffering from many diseases, including cognitive impairment and heart disease, to see if the drug can forestall comorbidities and death. They even named their trial after the drug, dubbing it Targeting Aging with Metformin.

The McGill researchers, working alongside scientists from the University of Edinburgh and the University of Montreal, understand that simply observing behavioral changes in mouse models of fragile X doesn’t guarantee that metformin is a wonder drug. Even though the safety of the drug is well-established—making it possible it could be fast-tracked into clinical trials for autism—they need to do more work to understand how exactly the drug is operating in the brain.

"It is a simple story in terms of the description of the corrections allowed by the drug," said Nahum Sonenberg, a biochemistry professor and co-senior author, in the release. "What is more complicated is the molecular mechanism, how exactly it works. We need to study, in the lab, what molecules metformin interacts with and what cellular functions are affected."