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Medicineworld.org: Gene Therapy Inhibits Epilepsy

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Gene Therapy Inhibits Epilepsy

Gene Therapy Inhibits Epilepsy
For the first time, scientists have inhibited the development of epilepsy after a brain insult in animals. By using gene treatment to modify signaling pathways in the brain, neurology scientists observed 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 scientists 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 especially 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 controlling brain activity. Prior animal research by Dr. Brooks-Kayal's group had observed that rats with epilepsy had lower levels of the alpha1 subunits of these receptors and higher levels of alpha4 subunits. Therefore, the scientists used gene delivery to alter the expression of the alpha1 subunit to see if this would have an effect on later seizure development.

To carry the gene that alters the expression of the protein, they used an adeno-associated virus vector, injected into the rats' brains. The scientists later injected the rats with pilocarpine, a drug that causes status epilepticus (SE), a convulsive seizure, shortly after injection.

They then reviewed the rats for later development of spontaneous seizures or epilepsy, which commonly occurs after an initial SE injury. Rats that had received the gene treatment had elevated levels of alpha1 proteins and either did not develop spontaneous seizures, or took three times as long to experience a spontaneous seizure, in comparison to rats that did not receive the delivered gene.

In this short-term study, said Dr. Brooks-Kayal, it was impossible to tell whether the increased alpha1 subunit levels were only suppressing seizures or whether they would permanently prevent epilepsy from developing.

"In people, an initial episode of SE or an injury such as severe head trauma is known to raise the risk of later developing epilepsy, so this study suggests that strategies aimed at modifying signaling pathways in the brain after such an insult may help prevent epilepsy," said Dr. Brooks-Kayal. "The approach would likely be different than in this proof-of-concept animal study that involved injecting agents directly into the brain. This study, does, however, lay the foundation for a potential drug treatment that might act on the same signaling pathways, to prevent epilepsy after a brain insult such as an episode of SE." .


Posted by: Daniel    Source




Did you know?
For the first time, scientists have inhibited the development of epilepsy after a brain insult in animals. By using gene treatment to modify signaling pathways in the brain, neurology scientists observed that they could significantly reduce the development of epileptic seizures in rats.

Medicineworld.org: Gene Therapy Inhibits Epilepsy

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