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Gene therapy inhibits epilepsy in animals

rolling brain activity. Previous animal research by Dr. Brooks-Kayal's group had found that rats with epilepsy had lower levels of the alpha1 subunits of these receptors and higher levels of alpha4 subunits. Therefore, the researchers 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 researchers later injected the rats with pilocarpine, a drug that causes status epilepticus (SE), a convulsive seizure, shortly after injection.

They then evaluated the rats for later development of spontaneous seizures or epilepsy, which usually occurs after an initial SE injury. Rats that had received the gene therapy had elevated levels of alpha1 proteins and either did not develop spontaneous seizures, or took three times as long to experience a spontaneous seizure, compared 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 therapy that might act on the same signaling pathways, to prevent epilepsy after a brain insult such as an episode of SE."


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Source:Children's Hospital of Philadelphia


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