Research

April 13, 2011

Strategy targets fragile X syndrome and epilepsy

Individuals with fragile X syndrome, the most common inherited form of intellectual disability, often develop epilepsy, but so far the underlying causes are unknown. Researchers have now discovered a potential mechanism that may contribute to the link between epilepsy and fragile X syndrome.

The protein that is missing in fragile X syndrome, FMRP, controls the production of a protein that regulates electrical signals in brain cells, scientists at the School of Medicine have found.

Individuals with fragile X syndrome tend to have a hyperexcitable nervous system, which can be displayed in several ways: hyperactivity, anxiety, increased sensory sensitivity, and epileptic seizures in 20 percent of all cases. The Emory team’s findings suggest that a therapeutic strategy against fragile X syndrome now being tested in clinical trials could also address this aspect of the disease.

“The link between fragile X syndrome and epilepsy was not well understood,” says senior author Gary Bassell, professor of cell biology and neurology. “This finding might provide a molecular explanation that could also give some clues on therapeutic strategies.”

The co-first authors of the paper are postdoctoral fellow Christina Gross and PhD candidate Xiaodi Yao. They and their colleagues found that in mice missing FMRP – a model for humans with fragile X syndrome – brain cells produce less of a protein called Kv4.2.

FMRP is known to regulate several genes, and it’s possible that changes in others besides Kv4.2 contribute to the development of epilepsy.

In laboratory tests, drugs that tamp down glutamate signaling could partially restore levels of the Kv4.2 protein in mice missing the fragile X protein. This suggests that drugs that act against glutamate signaling, which are now in clinical trials, could reduce hyperexcitability in humans with fragile X syndrome.

Another strategy could be to identify drugs that target the Kv4.2 protein’s function directly, Bassell says.

The research was supported by the National Institutes of Health and the National Fragile X Foundation.

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