Crucial steps towards Fragile X syndrome (FXS) treatment

June 2017: In a recent publication in Nature Medicine Dr Christos Gkogkas and his team present further insights of Metformin in a mouse model for FXS.

Fragile X syndrome (FXS) affects around 1 in 4,000 boys and 1 in 6,000 girls. It is the most common known cause of inherited intellectual disability, while patients are often co-diagnosed with autism. FXS is caused by mutations in the Fmr1 gene. Affected children have developmental delays that impair speech and language, problems with social interactions and are often co-diagnosed with autism, anxiety and seizures. At the moment there is no effective therapy for fragile X syndrome.

The lab of Christos Gkogkas is interested in understanding the neurobiological mechanisms underlying pathophysiology in neurodevelopmental disorders such as FXS.

They use rodent models, where they can genetically introduce the mutations found in FXS patients and recapitulate phenotypes which are reminiscent of FXS, such as social behaviour deficits and repetitive/stereotypic behaviours, accompanied by molecular and cellular changes.

Metformin is the most widely used anti-diabetic drug, and its safety and tolerability are well documented for more than 30 years. Metformin acts on cellular pathways which are known to go awry in FXS. One such pathway is that of protein synthesis, which is elevated in FXS patients.

The Team around Christos hypothesised that using metformin, they could perhaps inhibit the excessive protein synthesis. Using a mouse model for FXS, they discovered that metformin normalised protein synthesis and ameliorated or completely reversed several phenotypes in the Fmr1 mouse model.

Metformin is already approved by the UK’s Medicines and Healthcare products Regulatory Agency and the US Food and Drug Administration as a therapy for type 2 diabetes.

If metformin clinical trials in people with FXS are successful then the drug could be quickly repurposed for FXS treatment, certainly faster than a brand new medication. Moreover, the use of metformin could be expanded to treat other forms of autism.


Related Links

Publication in Nature Medicine

Christos Gkogkas' research profile