Fragile X Syndrome Reversed

Jun 26, 2020 by Iris Dawn Tabangcora



MIT scientists have successfully reversed the symptoms of Fragile X in mice using a small-molecule compound. Fragile X is an inherited condition caused by a mutation in the FMR1 gene leading to intellectual disability and autism. This discovery paves way for potential new strategies in treating Fragile X syndrome which can also involve a variety of manifestations such as epilepsy, light and noise hypersensitivity, and hand-flapping, among others.

In the mouse study, researchers showed that inhibiting the GSK3 alpha enzyme reversed many of the behavioral and cellular features of Fragile X.  This treatment may also be of benefit to Alzheimer’s patients, another condition in which GSK3 is implicated.

For two decades Fragile X has been a subject of study by a team led by Mark Bear, the Picower Professor of Neuroscience at MIT. In one of their previous studies, they have shown that protein synthesis is stimulated by a receptor called metabotropic glutamate receptor 5 (mGluR5). mGluR5 becomes overactive when FRMP is lost and this accounts for the symptoms seen in Fragile X syndrome. However, compounds that could reverse mGluR5 were never successful in clinical trials. This prompted the group to research other possible target molecules.

As for side effects, exploration showed that GSK3 alpha inhibitors lack the side effects that mGluR5 inhibitors had which caused it to fail clinical trials. These side effects include hallucination and resistance to long-term treatment. 

Aside from Alzheimer’s disease, a study conducted last year showed that selective GSK3 inhibitors could be effective against acute myeloid leukemia.

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