New 'systems genetics' study identifies possible target for epilepsy treatment

A single gene that coordinates a network of about 400 genes involved in epilepsy could be a target for new treatments, according to research. A team from Imperial College London developed novel computational and genetics techniques to systematically analyze the activity of genes in epilepsy. Published in Nature Communications, the study is the first to apply this 'systems genetics' approach to epilepsy.

The researchers studied samples of brain tissue removed from patients during neurosurgery for their epilepsy. Starting from these samples, they identified a gene network that was highly active in the brain of these patients, and then discovered that an unconnected gene, Sestrin 3 (SESN3), acts as a major regulator of this epileptic gene network. This is the first time SESN3 has been implicated in epilepsy and its coordinating role was confirmed in studies with mice and zebrafish.

Using surgical samples of brain tissue provides a unique opportunity to study how genes are coordinated in the brains of people with epilepsy. Patients with severe temporal lobe epilepsy who do not respond to medication can undergo surgery to remove part of the brain to relieve their seizures. The research was able to use brain tissue samples donated by 129 patients to analyze the genetic and functional activity underlying their epilepsy.

Co-senior author of the paper, Michael Johnson, PhD, says: “This study is proof-of-concept for a new scientific approach in epilepsy. Existing epilepsy medications are symptomatic treatments only; that is they act to suppress the seizures but they don't treat the underlying disease. Consequently, we find that existing medications don't work in about one-third of people with epilepsy. Here we have taken a new approach, and identified a network of genes underlying the epilepsy itself in these patients and mapped its control to a single gene, SESN3. This offers hope that new disease-modifying therapies can be developed for the treatment of epilepsy itself.”