Common Genetic Variants May Explain Drug Resistance in Epilepsy: Global Study

New Delhi: A new international study has identified common genetic variants that may explain why some individuals with focal epilepsy do not respond to standard antiseizure medications. The research, led by scientists at University College London (UCL) and the University of Texas Health Science Center at Houston (UTHealth Houston), offers critical insights into the genetic basis of drug-resistant epilepsy.

Focal epilepsy, the most prevalent form of epilepsy, involves seizures that originate in a specific region of the brain. While antiseizure medications are the primary treatment, nearly one in three individuals with epilepsy—approximately 20 million people globally—experience drug resistance, continuing to have seizures despite treatment. This condition is associated with increased health risks, including a higher likelihood of sudden unexpected death in epilepsy (SUDEP) and elevated healthcare costs.

Published in EBioMedicine, the study examined the genetic data of 6,826 individuals with epilepsy. Researchers compared the genomes of 4,208 people with drug-resistant epilepsy against 2,618 individuals whose seizures were effectively controlled with medication. The findings revealed two key genetic variants—located in the CNIH3 and WDR26 genes—were significantly associated with drug resistance.

The CNIH3 gene is involved in regulating brain receptors, while WDR26 plays a role in various cellular processes. Variants in these genes appear to influence how individuals respond to antiseizure drugs, making them more likely to develop resistance.

“These findings highlight why some people experience seizures that do not respond to current treatments,” said Professor Sanjay Sisodiya of UCL’s Queen Square Institute of Neurology. Assistant Professor Costin Leu from UTHealth Houston added that these common variants, despite being widespread in the general population, have a strong impact on treatment outcomes.

Importantly, these genetic markers can be identified at the onset of epilepsy, potentially enabling early prediction of drug resistance. This could help avoid exposing patients to ineffective treatments and their associated side effects, paving the way for more personalized and effective epilepsy care. The study also strengthens the case for expanding genetic testing and developing future therapies tailored to polygenic forms of epilepsy.