By using gene therapy to modify signaling pathways in the brain, researchers found that they could significantly reduce the development of epileptic seizures in rats.
“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,” said Amy Brooks-Kayla, a pediatric neurologist at The Children’s Hospital of Philadelphia.
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.
GABA(A) receptors are made up of five subunits – proteins that play important roles in brain development and in controlling brain activity. Previous animal research 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.
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, researchers said, it was impossible to tell whether the increased alpha1 subunit levels were only suppressing seizures or whether they would permanently prevent epilepsy from developing.
The researchers said that testing gene therapy in people would likely be different than in this proof-of-concept animal study that involved injecting agents directly into the brain.