080210xf's Blog

L'X fragile sera vaincu | Fragile X will be conquered

Researchers Link Fragile X Syndrome, Epilepsy

By Mallika Manyapu, Emorywheel.com |

Emory researchers have discovered a connection between fragile X syndrome — the most common form of mental impairment — and epilepsy, according to an April 12 University press release.

Fragile X syndrome is characterized by a lack of the protein Fragile X Mental Retardation Protein (FMRP), which regulates neural firing, leaving neurons hyperexcitable and overactive in its absence, said Gary Bassell, a principal investigator and professor in the School of Medicine. These excessive neural impulses lead to repeated seizures or epilepsy, according to Bassell.

The researchers found that FMRP is responsible for the production of another vital protein, Kv4.2, which regulates electrical signals in the brain. However, a lack of FMRP will cause brain cells to produce less Kv4.2, which causes many proteins and neural processes to be continuously active and can lead to impaired learning, seizures and epilepsy.

“Everything is heightened and exaggerated for a person with fragile X,” Bassell said.

Researchers conducted the study using genetically engineered mice to serve as animal models for fragile X syndrome. The researchers also worked with 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP), a drug that inhibits particular neural processes such as glutamate signaling.

Because glutamate signaling removes Kv4.2 from certain pathways, drugs such as MTEP that inhibit this process keep higher levels of Kv4.2 in the appropriate channels to control neural impulses, Bassell said.

MTEP provides particular therapeutic effects in the genetically-engineered mice, showing restored levels of the Kv4.2 protein in mice missing the fragile X protein FMRP. This means that drugs such as MTEP could potentially reduce the severe epileptic effects of fragile X, he said.

According to Bassell, this study is particularly important to future clinical trials and treatments of fragile X syndrome because at least 20 percent of people with diseases like fragile X have epilepsy or epileptic symptoms.

“We were interested in the molecular basis for why patients with fragile X and other autistic diseases had epilepsy,” Bassell said. “Drugs like MTEP may be used in clinical trials to treat fragile X, but we may want to design direct drugs that specifically target the essential molecule.”

Their conclusions were published on April 13 in The Journal of Neuroscience. The research was funded by the National Institutes of Health and the National Fragile X Foundation.

The primary authors were Christina Gross, a postdoctoral fellow in Bassell’s lab in the of Department of Cell Biology and Neurology, Xiaodi Yao, a Ph.D. candidate, and Dan Pong (’09C).

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