RECENT research has identified two novel genes, DYRK1A and EGFR, as being associated with genetic mutations linked to epilepsy, offering potential biomarkers and new therapeutic avenues.
Epilepsy, a neurological condition affecting approximately 3.4 million people in the United States, is particularly challenging for the one-third of patients with drug-resistant forms of the disorder. Researchers from UTHealth Houston, led by Dennis Lal, Ph.D., analysed 1,386 human brain tissue samples from epilepsy surgery patients to identify somatic variants—DNA mutations occurring after conception that can only be detected in brain tissue. The findings aim to improve the understanding of epilepsy’s genetic basis and explore new treatment strategies.
Using ultra-deep sequencing techniques (exceeding 1600x coverage), the study confirmed four well-established gene-disease associations, provided evidence for eight previously unsupported links, and discovered two new genes, DYRK1A and EGFR, tied to epileptic brain lesions. These mutations were observed to interact with pathways targeted by FDA-approved cancer drugs, highlighting therapeutic repurposing opportunities. Unlike cancer cells, the neurons affected in epilepsy do not replicate, a key distinction that makes drug repurposing feasible. The research also demonstrated the potential for these genetic markers to serve as diagnostic tools, particularly for patients undergoing epilepsy surgery, pending wider clinical application of brain tissue testing.
The findings carry significant implications for clinical practice, potentially paving the way for tailored interventions for drug-resistant epilepsy. While the insights enhance diagnostic precision, they also provide a foundation for developing treatments targeting the root causes of epilepsy. Future research should focus on translating these findings into clinical workflows and further investigating how existing drugs can be adapted for use in epilepsy care. This study marks a step towards improving the quality of life for patients and caregivers by addressing epilepsy at its most fundamental biological level.
Katrina Thornber, EMJ
Reference
Boßelmann CM et al. Analysis of 1386 epileptogenic brain lesions reveals association with DYRK1A and EGFR. Nat Commun. 2024;15:10429.
