Can Your Genes Predict Epilepsy Treatment Failure? New Study

A new international study led by scientists at University College London (UCL) and UTHealth Houston has found that some people with focal epilepsy may be genetically predisposed to not respond to commonly prescribed seizure medications.

Understanding Focal Epilepsy

Focal epilepsy is the most common form of epilepsy, where seizures begin in a specific part of the brain. These seizures are typically treated with antiseizure medications. However, for around one in three people with epilepsy an estimated 20 million people globally these medications don’t work effectively. This condition is known as drug-resistant epilepsy.

Drug resistance in epilepsy not only makes seizures harder to control but also increases the risk of serious health complications, including sudden unexpected death in epilepsy (SUDEP). It also places a heavier burden on healthcare systems due to higher medical costs and the need for alternative treatments.

What the Study Found

Until now, it was not well understood why certain individuals do not respond to antiseizure medications. But in this large-scale genetic study published in eBioMedicine, researchers found that certain common genetic variants may increase the risk of drug resistance in people with focal epilepsy.

The team used genetic data from two large projects EpiPGX and Epi25 analyzing the genomes of 6,826 people with epilepsy. They compared two groups:

• 4,208 people with drug-resistant epilepsy
• 2,618 people whose seizures were well controlled with medication

The analysis revealed that genetic variations in two genes CNIH3 and WDR26 were more common in people who did not respond to seizure medications. The CNIH3 gene is involved in brain receptor function, while WDR26 plays a role in various cellular processes.

A Step Toward Personalized Epilepsy Treatment

Professor Sanjay Sisodiya of the UCL Queen Square Institute of Neurology, the study’s senior author, said the research offers fresh insight into the causes of drug-resistant seizures in some individuals. He added that these findings may help doctors in the future to predict early on who is more likely to have drug resistance, allowing for more tailored treatment plans.

What makes this discovery particularly valuable is that these genetic markers can be identified at the time of diagnosis, rather than after years of trying different medications without success. This could help patients avoid unnecessary side effects from ineffective treatments.

Expanding the Scope of Genetic Testing

Lead author Dr. Costin Leu, now at UTHealth Houston, emphasized that these common genetic changes are usually overlooked in current clinical testing. However, they have a significant impact on how patients respond to treatment.

He also highlighted the importance of addressing polygenic epilepsy, a type caused by multiple genes. As this is the most widespread form of genetic epilepsy, using genetic information to guide treatment could improve outcomes for a large number of patients who currently don’t benefit from targeted therapies.

Conclusion

This groundbreaking study marks a major step toward personalized medicine in epilepsy care. By identifying genetic factors linked to treatment resistance, doctors may soon be able to predict which patients need alternative therapies from the start. This could lead to more effective management of epilepsy, fewer side effects, and a better quality of life for millions around the world.

Source: Inputs from various media Sources