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Gene therapy inhibits epilepsy in animals

For the first time, researchers have inhibited the development of epilepsy after a brain insult in animals. By using gene therapy to modify signaling pathways in the brain, neurology researchers found that they could significantly reduce the development of epileptic seizures in rats.

"We have shown that there is a window to intervene after a brain insult to reduce the risk that epilepsy will develop," said one of the lead researchers, Amy R. Brooks-Kayal, M.D., a pediatric neurologist at The Children's Hospital of Philadelphia and associate professor of Neurology and Pediatrics at the University of Pennsylvania School of Medicine. "This provides a 'proof of concept' that altering specific signaling pathways in nerve cells after a brain insult or injury could provide a scientific basis for treating patients to prevent epilepsy."

Dr. Brooks-Kayal and Shelley J. Russek, Ph.D., of Boston University School of Medicine were senior authors of the study in the Nov. 1 Journal of Neuroscience.

Working in a portion of the brain called the dentate gyrus, the researchers focused on one type of cell receptor, type A receptors, for the neurotransmitter gamma-aminobutyric acid (GABA). When GABA(A) receptors are activated, they inhibit the repetitive, excessive firing of brain cells that characterizes a seizure. Seizures are thought to occur, at least in part, because of an imbalance between two types of neurotransmitters: the glutamate system, which stimulates neurons to fire, and the GABA system, which inhibits that brain activity.

GABA's inhibitory role is considered particularly important in the dentate gyrus because the dentate gyrus acts as a gateway for brain activity into the hippocampus, an area that is critical to generating seizures in temporal lobe epilepsy, the most common type of epilepsy in children and adults.

GABA(A) receptors are made up of five subunits--proteins that play important roles in brain development and in cont
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Source:Children's Hospital of Philadelphia


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