Fragile X syndrome is a genetic disease caused by defects in the Fragile X Mental Retardation 1 gene (FMR1), which triggers excess production of protein in the brain, as well as dysregulated connections between neurons and changes in behavior. The condition leads to impairments in speech and language, behavior and social interaction. It affects about 1 in 5,000 boys and 1 in 6,000 girls and is often co-diagnosed with autism, anxiety disorders and seizures.

Metformin, the most widely used drug to treat type 2 diabetes, could potentially be used to treat symptoms of Fragile X syndrome, an inherited form of intellectual disability and a cause of some forms of autism.

A new study has found that metformin improves social, behavioral and morphological defects in Fragile X mice.

Fragile X mice - animals that display symptoms associated with the disease such as increased grooming and decreased socialization - showed normal brain connections and behavioral patterns after 10 days of injection with metformin.

'Wonder drug' In the past few years, metformin has generated extensive interest for its potential in treating numerous health problems such as cancer, cardiovascular diseases, neurological diseases and aging.

The study also established that metformin restores some of the molecular pathways disrupted in the absence of the FMR1. Trinucleotide repeat expansions in FMR1 abolish FMRP expression, leading to hyperactivation of ERK and mTOR signaling upstream of mRNA translation. Authors show that metformin, rescues core phenotypes in Fmr1^−/y mice and selectively normalizes ERK signaling, eIF4E phosphorylation and the expression of MMP-9. 

The next step will be to understand the drug's exact role in these pathways.

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

Moreover, the drug could be tweaked "to be more efficient than metformin" and repurposed, for example, for other disorders, author added.

http://www.mcgill.ca/newsroom/channels/news/diabetes-drug-may-help-symptoms-autism-associated-condition-268128

https://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4335.html