New insights on why epilepsy develops, potential treatments in world’s largest genetic study  

Published today in Nature Genetics, this research advances our understanding of why epilepsy develops and could inform the development of new epilepsy treatments. The research was produced by the International League Against Epilepsy (ILAE) Consortium on Complex Epilepsies.

Epilepsy is a common brain disorder estimated to effect more than 50 million people worldwide, where nerve cell activity in the brain is disturbed, causing seizures. It has a genetic component that sometimes runs in families.

In this study, researchers compared the DNA from almost 30,000 people with epilepsy to the DNA of 52,500 people without epilepsy from around the world. The differences between the two groups highlighted areas of DNA that may be involved in the development of epilepsy.

The researchers identified 26 distinct areas in our DNA that appear to be involved in epilepsy, including 19 that are specific to a particular form of epilepsy called ‘genetic generalised epilepsy’ (GGE). They also identified 29 genes that they believe are probably contributing to epilepsy within these DNA regions.

The researchers also found the genetic picture was different when comparing distinct types of epilepsy, providing clues as to why different epilepsy syndromes exist.

The results also lead researchers to believe that proteins that carry electrical impulse across the gaps between neurons in our brain could make up some of the risk for generalised forms of epilepsy.

University of Melbourne Laureate Professor Samuel Berkovic co-led the study and said: “Gaining a better understanding of the genetic underpinnings of epilepsy is key to developing new therapeutic options and consequently a better quality of life for the over 50 million people globally living with epilepsy.”

Karen Oliver, PhD candidate at WEHI and University of Melbourne Research Fellow in the Epilepsy Centre, who was the ILAE Consortium coordinator and part of the data analysis team, said: “The discoveries we report on here could only be achieved through international collaboration, on a global scale.

“We are proud of how the global community of scientists working to better understand the genetics of the epilepsies have pooled resources and collaborated effectively, for the benefit of people impacted by the condition.”

The researchers also found many of the current medications for epilepsy work by targeting the same epilepsy risk genes highlighted in their study.

The researchers identified some epilepsy risk genes that are known to be targeted by existing treatments for other conditions, offering potential avenues for further epilepsy treatment research.

Professor Gianpiero Cavalleri from RCSI University of Medicine and Health Sciences, Dublin, one of the co-leaders of the project, said: “This identification of epilepsy associated genetic changes will allow us to improve diagnosis and classification of different epilepsy subtypes. This in turn will guide clinicians in selecting the most beneficial treatment strategies, minimising seizures.”

More than 300 researchers based across Europe, Australia, Asia, South America and North America, worked together as part of the International League Against Epilepsy (ILAE) Consortium on Complex Epilepsies to produce this research.

The ILAE Consortium was established by researchers in 2010, recognising that the complexity of genetic and environmental factors underlying epilepsy required research across substantial datasets and unprecedented collaboration on an international scale.

“Undertaking such a comprehensive study is a remarkable achievement. The challenge now is to translate the findings of this research to improve the lives of people with epilepsy,” Prof Cavalleri said.

Contributing co-author WEHI Professor Melanie Bahlo said: “With this study, we have bookmarked parts of our genome that should be the major focus of future epilepsy research.

“It will form the basis for further work looking at the molecular pathways involved in seizure generation, neuronal dysfunction and altered brain activity.”

President of the International League Against Epilepsy Professor Helen Cross said: “This is a major milestone for the ILAE Consortium on Complex Epilepsies, demonstrating what can be achieved when scientists openly collaborate and share data from across the world. The outputs are wide-reaching and applicable to epilepsy patients globally.”

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