Background

Treatment of epilepsy remains a clinical challenge with approximately 30% of patients not responding to current anti-seizure medications used in the clinic. Research by our group has identified a specific cell membrane receptor expressed throughout the brain termed P2X7 receptor as potential novel target. While we, and others, have shown that manipulating this receptor influences seizures and epilepsy, these experiments have been restricted to pre-clinical rodent models and no research has been done using human cellular models, critical to advance findings towards a clinical application.

Research

Here, we used human induced pluripotent stem cells (hiPSCs)-derived neurons and tested the seizure suppressive actions of several P2X7 receptor blocking drugs developed for a clinical application. hiPSC cultures, when stimulated, showed epileptiform seizure activity, which was suppressed in the presence of P2X7 receptor antagonists. Notably, P2X7 receptor antagonists potentiated the actions of commonly used anti-seizure medications.

Potential Impact

This study has provided evidence for the anti-epileptic potential of P2X7 receptor antagonists using a model system of human cells. Our findings suggest, therefore, that P2X7 receptor-based treatments may be a viable novel adjunctive therapy for drug-refractory epilepsy.