Researchers at UTHealth Houston have identified two genes linked to epilepsy, offering potential pathways for personalized treatment. The study, published in Nature Communications, was led by Dennis Lal, PhD, director of the Center for Neurogenetics and associate professor of neurology at McGovern Medical School at UTHealth Houston.
The team analyzed 1,386 human brain tissues from individuals undergoing epilepsy surgery to identify somatic variants—DNA changes occurring after conception that can only be detected in brain tissue. According to the CDC, epilepsy affects about 3.4 million people in the U.S., with one-third experiencing drug-resistant forms. By linking specific genetic mutations to epilepsy, this research provides a framework for developing therapies targeting the disorder's root causes.
The study discovered two novel genes, DYRK1A and EGFR, associated with epileptic brain lesions. "Discovering these genes not only helps us better understand the biology behind epilepsy but also reveals specific traits in tissues, making them valuable tools for diagnosing the condition," Lal stated.
Lal's team confirmed four established gene-disease associations and found evidence for eight more. Once clinical testing of brain tissue post-surgery becomes available outside research settings, these findings could help address causes of drug-resistant epilepsy.
The project also highlighted that many genes linked to variants interact with biological pathways targeted by FDA-approved cancer drugs. Although epileptic lesions share genetic similarities with tumors, they differ significantly as neurons do not replicate like cancer cells do. This opens possibilities for repurposing existing cancer drugs for treating epilepsy.
"For those with epilepsy, their caregivers, and health care providers, our research represents a step closer to understanding epilepsy at its most fundamental level while improving patients’ quality of life," said Lal.
Co-authors included Christian Bosselman from Universitätsklinikum Tübingen; Costin Leu and Tobias Brünger from UTHealth Houston; Lucas Hoffman from the University of Washington; Katja Kobow from Universitätsklinikum Erlangen; Imad Najm from the Cleveland Clinic; and Ingmar Blumcke from Universitätsklinikum Erlangen – Institute of Neuropathology.
