Genetic study suggests possible means to identify drug resistant epilepsy
21 Apr 2025
Identifiying ‘genetic signatures’ could enable medical experts to determine which epilepsy sufferers are most likely to certain seizure medications, suggests a new report.
Writing in eBioMedicine, researchers say this might help ensure patients avoid being given inappropriate treatments and unnecessarily enduring associated side effects.
Senior author Sanjay Sisodiya, professor at London’s UCL Queen Square Institute of Neurology said the findings of our study offered new insights about why some people have seizures that are resistant to existing medications.
“Further work may enable doctors to use this information to help predict who may turn out to have drug-resistant epilepsy and may help doctors develop newer treatments for the condition,” he said.
While anti-seizure medications are normally prescribed, the researchers say that as many as a third of all the 20 million people with epilepsy may be drug resistant.
In addition to the difficulties this presents for treatment, drug resistance is associated with a greater risk of sudden death.
Sisodiya and his colleagues and collaborators examined whether genetic factors accounted for resistance amongst some people with focal epilepsy – the most common form of the condition, involving seizures that begin in a single section of the brain.
They interrogated data collected from the international project on epilepsy pharmacogenetics, EpiPGX, as well as Epi25, the largest sequencing study in epilepsy. Genetic variations were examined in nearly 7,000 sufferers, roughly 60% of whom were resistant, with the remainder having conditions that were controlled by medications.
This revealed specific variations in the genes CNIH3 and WDR26 coincided with a higher risk of drug resistance.
First author, assistant professor Costin Leu of UTHealth Houston and previously UCL Queen Square Institute of Neurology pointed out that polygenic epilepsy – influenced by multiple genes – represented the vast majority of all genetic epilepsy cases.
“Our study provides the first evidence that common genetic variants — usually not addressed in clinical genetic testing — significantly contribute to drug resistance in epilepsy,” said Leu.
“Recognising these genetic variants, which are frequent in the general population yet strongly influence treatment outcomes, underscores the need to expand genetic testing and future therapies to address polygenic epilepsy.”
Pic: Maxim Berg
