Gene Therapy Prevents Seizures in Rat Model of Epilepsy

Neurologists working with a rat model have used gene therapy to prevent the development of epileptic seizures after brain injury.

Investigators at the Children's Hospital of Philadelphia (PA, USA) employed an adeno-associated virus vector to insert the alpha-4 subunit gene (GABRA4) promoter into the brains of rats. This gene therapy was intended to stimulate the production of GABAA receptor alpha-1 subunits in the hippocampal dentate gyrus region of the animals' brains. Previous studies had demonstrated reduced expression of GABR alpha-1 subunits and increased expression of alpha-4 subunits in dentate gyrus of epileptic rats compared with controls.

After successful acclimation of the transplanted gene, the rats were injected with pilocarpine, a drug that caused the animals to experience an epileptic seizure (status epilepticus or SE). Results published in the November 1, 2006, issue of the Journal of Neuroscience revealed that enhanced alpha-1 expression in the dentate gyrus resulted in a threefold increase in mean seizure-free time after SE and a 60% decrease in the number of rats developing epilepsy (recurrent spontaneous seizures) in the first four weeks after SE.

"We have shown that there is a window to intervene after a brain insult to reduce the risk that epilepsy will develop,” explained senior author Dr. Amy R. Brooks-Kayal, associate professor of pediatric neurology at the Children's Hospital of Philadelphia. "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. This study lays 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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