Metformin Shows Promise as Rare Disease Treatment

Metformin, a drug commonly used drug to treat type 2 diabetes, works by reducing the excessive release of blood sugar. The results of a new study published by Nature Medicine suggest that metformin may also be used to treat the social, behavioral, and morphological symptoms of Fragile X syndrome.

This condition is a rare genetic disease caused by defects in the Fragile X Mental Retardation 1 gene (FMR1). Fragile X syndrome results in an excess production of FMR1 and dysregulates connections between neurons and changes behavior.

Patients with Fragile X syndrome frequently have impaired speech, language, behavior, and social interaction. The condition is generally co-diagnosed with autism, anxiety, and seizures. Approximately 60% of children with Fragile X syndrome are also diagnosed with autism. There is currently no cure for the condition.

In the study, the authors found that mouse models of Fragile X syndrome displayed normal brain connections and behavior patterns after only 10 days of metformin injections.

"This is some of the most exciting research work in my career, as it offers great promise in treating a pernicious genetic disease for which there is no cure," said co-senior study author Nahum Sonenberg, PhD.

Since metformin has been widely used over the past few decades, its safety profile is well-documented. Because metformin has already been approved by the FDA, clinical trials would be expedited. Common side effects of metformin include diarrhea, abdominal pain, and cramping, which can be manageable.

In recent studies, the drug has showed promise in treating cancer, heart diseases, neurological conditions, and aging. A previous study discovered that metformin may change the mechanisms of cancer cells by inhibiting their source of nutrients, making it an effective treatment option for the disease.

"Basically, it's something like a wonder drug," Dr Sonenberg said.

The new study suggests that metformin may also be used to treat autism spectrum disorders, which also do not have a cure.

"We mostly looked at the autistic form of behaviour in the Fragile X mouse model," said co-lead study author Ilse Gantois, PhD. "We want to start testing other mouse models to see if the drug could also have benefits for other types of autism."

Additionally, the authors discovered that metformin was able to restore some of the pathways disrupted by the deficiency of FMR1, according to the study. They next plan to determine how metformin’s exact role in the pathways.

The investigators believe that metformin could be altered to become more effective and repurposed for other conditions.

"It is a simple story in terms of the description of the corrections allowed by the drug," Dr Sonenberg said. "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."