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26-01-2015 | New 'systems genetics' study identifies possible target for epilepsy treatment

26 January 2015
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A single gene that coordinates a network of about 400 genes involved in epilepsy could be a target for new treatments, according to research.

Instead of studying individual genes, which has been the usual approach in epilepsy to date, researchers from Imperial College London developed novel computational and genetics techniques to systematically analyse the activity of genes in epilepsy. Published in Nature Communications, the study is the first to apply this 'systems genetics' approach to epilepsy.

Dr Enrico Petretto, from the Medical Research Council (MRC) Clinical Sciences Centre at Imperial College London and co-senior author of the study, said: "Systems genetics allows us to understand how multiple genes work together, which is far more effective than looking at the effect of a gene in isolation. It's a bit like trying to tackle a rival football team. If you want to stop the team from playing well, you can't just target an individual player; you first need to understand how the team plays together and their strategy. Likewise in systems genetics we don't look at just one gene at a time, but a network or team of genes and the functional relationships between them in disease.

"After understanding how the team plays together, a possible approach to beating a strong side is then to identify a major control point- say the captain or the coach -- who co-ordinates the players. This is like our 'master regulator gene', which in this case is SESN3. If we can develop medication to target this gene in the brain, then the hope is that we could influence the whole epileptic gene network rather than individual parts and in turn achieve more effective treatments."

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. Our research was able to use brain tissue samples donated by 129 patients to analyse the genetic and functional activity underlying their epilepsy.

Co-senior author of the paper, Dr Michael Johnson from Imperial's Department of Medicine, said: "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 supress 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. For more go to Science Daily

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