Cenobamate reduces epileptiform activity in the ex vivo F98 rat glioma model

Epileptic seizures are a common clinical sign in patients suffering from high-grade glioma. In addition to therapeutic interventions aiming to prolong the remaining lifespan, maintaining quality of life is a cornerstone of current treatment concepts. Consequently, anticonvulsants are frequently applied to keep seizures at bay, but drug resistance is still a challenge. There is a need for new anticonvulsants to address this issue. Therefore, for the first time, we evaluated the efficacy of cenobamate, a novel anticonvulsant shown to inhibit persistent sodium currents and modulate GABA_A receptor function, in a preclinical model of glioma-associated epilepsy. In our study, we used cortical slices from naive Fischer rats and animals with orthotopically implanted F98 tumors.

To study the effect of cenobamate (60 and 120 μmol/L), we recorded local field potentials and evoked spontaneous network deflections using an acute disinhibition solution. To analyze seizure-like events (SLEs), we employed a deep learning approach, further supported by power spectral density (PSD) analysis.

Cenobamate attenuated the proportion of recording time occupied by SLEs, mainly by reducing their duration in slices of both sham-operated and F98 tumor-bearing animals. Additionally, the spike load within SLEs was diminished by the anticonvulsant. The PSD analysis confirmed the reduction of spike frequencies abundant in seizure-like events.

Our data show that cenobamate effectively reduced the epileptic phenotype in glioma-bearing brain slices. We hence suggest that cenobamate may effectively contribute to seizure control in tumor-associated epilepsy.