Epileptic seizures nearly vanish after people receive experimental gene therapy

An experimental treatment sharply reduced seizures in three adults whose epilepsy had resisted medication. Each had unilateral hippocampal sclerosis, a scarring condition linked to seizures, and had lived with epilepsy for 10 to 25 years. Before treatment, they experienced at least two seizures per month on average. After receiving the therapy, their monthly seizure counts fell by more than 90%, and none experienced serious side effects during the early-stage trial.

The approach combines gene therapy with a drug to give researchers control over the treatment’s effect. Surgeons infused adeno-associated virus 9 directly into the small brain region generating each person’s seizures. The virus delivered a gene that makes targeted excitatory neurons produce receptors responsive to clozapine. Taking the drug activates those receptors, dampening the neurons’ activity and, in turn, the abnormal electrical signals behind seizures. The results suggest this “chemogenetic” strategy could offer a new option for people whose epilepsy does not respond to existing drugs. However, the trial included only three people, so its benefits and risks remain uncertain. Clozapine, an antipsychotic used to activate the therapy, can cause cardiovascular and other serious problems at high doses, raising questions about long-term use and the need for safer drug alternatives.