Epilepsy: Potential clues on causes revealed in new DNA study

  • 26 areas of DNA have been identified as being involved in the development of epilepsy.
  • The research is the largest genetic study of its kind and involved more than 150 researchers across the world.
  • Experts say being able to better understand the genetic underpinnings of epilepsy could lead to more targeted treatments.

Specific changes in DNA may increase the risk of developing epilepsy.

That’s according to research published in the journal Nature Genetics.

In the study, researchers identified 26 areas of DNA involved in the development of epilepsy in addition to 29 genes that are likely contributing to epilepsy within those areas.

“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,” Gianpiero Cavalleri, PhD, a co-author of the study and a professor of human genetics at RCSI School of Pharmacy and Biomolecular Science and Deputy Director of the SFI FutureNeuro Research Centre, said in a press statement.

“The discoveries we report on here could only be achieved through international collaboration, on a global scale,” he added. “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 the condition.”

A global collaboration for epilepsy research

The new research is the largest genetic study of its kind and involved more than 150 researchers in North America, South America, Europe, Australia and Asia.

As part of the study, the researchers compared DNA from nearly 30,000 people living with epilepsy alongside DNA from more than 52,500 people without the condition.

The scientists were able to identify 26 distinct changes to the DNA in people living with epilepsy. They were also able to identify 19 changes in DNA that are specific to a type of epilepsy called genetic generalized epilepsy (GGE).

“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” Dr. Colin Doherty, a co-author of the study as well as a consultant neurologist at St James’s Hospital in Dublin and clinical investigator at the SFI FutureNeuro Centre, said in a press statement.

As part of the study, the researchers said they were able to demonstrate that many medications currently used in the treatment of epilepsy work by targeting the genes they identified as increasing the risk of epilepsy.

They were also able to use their data to suggest alternative drugs that are currently used for other conditions but are also known to target some of the genes identified in the study.

The unknowns of epilepsy

Experts say the study represents an important step forward in the understanding of epilepsy.

“The reason why it’s a big deal is first of all, we don’t really understand clearly what are the causes of epilepsy and how it comes about. This study goes a long way to provide some understanding, like the biology behind the formation of epilepsy. Those genetic differences leads the researcher to postulate about some proteins and some molecules that might be involved in epilepsy in all these patients,” Dr. Jean-Philippe Langevin, a neurosurgeon and director of Restorative Neurosurgery and Deep Brain Stimulation Program for Pacific Neuroscience Institute at Providence Saint John’s Health Center in California, told Medical News Today.

“The more we understand about the genetics, it’s also going to provide new targets for future therapy. The more we understand the biology and the physiology of the disease, the better we can target and offer treatments for the patients,” Langevin added.

Electricity in the brain and epilepsy

Epilepsy is a brain disorder in which neurons, a type of nerve cell located in the brain, can sometimes send the wrong signals. This causes seizures.

When a seizure occurs, there is an increase in excessive electrical activity in the brain. This may cause involuntary sensations, movements and behavior.

“In the olden days, if you were in Salem, Massachusetts, and you had a seizure, you would have been burned as a witch… because people had no idea that you could have electricity in your brain. We still don’t know what makes a seizure start, we still don’t know what makes a seizure stop. Neuroscience remains complicated in the year 2023. Our knowledge when it comes to neuroscience, is still very basic and benign,” Dr. Clifford Segil, a neurologist at Providence Saint John’s Health Center in California, told Medical News Today.

“If we have an understanding of the genetics of epilepsy, it will help patients who have seizures get better medical treatments,” he explained. “The mainstay of treating patients with seizures is to give them anti-seizure medications, or anti-epileptic drugs. The drugs, by definition make your brain electricity fire slower because a seizure is an uncontrollable burst of electricity. And these medications can cause people to be slower fatigued. With a genetic understanding of seizures, we would have a molecular basis of what is causing the seizure. So a gene test will help an epileptologist determine which drugs to use in a perfect world.”

Precision medicine for epilepsy

About 3.4 million people in the United States live with epilepsy and there is no single treatment that works for every person who has the condition.

Experts say this research is another step toward precision medicine, an approach in which treatments are tailored to the individual based on their genetics, lifestyle, and environment.

“The core thing to understand and to take from this article is that we are moving or trying to move to what we call personalised medicine. The significance is that when we identify specific genetic types of epilepsy, some respond differently to different medications,” Dr. Dawn Eliashiv, a professor of neurology and Co-Director of the UCLA Seizure Disorder Center in California, told Medical News Today.

“It brings us into the ushering of what we call precision medicine and personalized medicine,” she said. “That’s I think the vision that should make people with epilepsy look forward to a time when the drug regimens and the treatment regimens and also the research focus on candidates will be driven specifically by our genetic knowledge.”

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