Long‐term treatment with carbamazepine restores cognitive abilities in a mouse model of <i>KCNQ2</i> developmental and epileptic encephalopathy

Auteurs

Louis J, Doudka N, Félix MS, Spiga Ghata A, Espanet C, Guilhaumou R, Milh M, Villard L

Les auteurs en lien sont membres de l'INS.

Équipes

TNG

Résumé

Abstract Objective Carbamazepine is the first line treatment for patients affected by KCNQ2 developmental and epileptic encephalopathy. It is efficient to reduce or stop seizures in this context. However, its effect on the neurodevelopmental outcomes is debated. The aim of this study was to evaluate the efficacy of long‐term oral administration of carbamazepine in a mouse model of Kcnq2 dysfunction. Methods Mice were treated at weaning and during 70 days. The impact on seizures was measured, and blood samples were collected every week. At 3 months of age, all mice were tested using the Water T‐maze and Barnes maze tests to evaluate their cognitive abilities. Brain tissue was collected to measure carbamazepine and carbamazepine‐epoxide concentrations. Results After 70 days of carbamazepine treatment, the impact on seizures was strong in the Kcnq2 ‐DEE mice, with 1 out of 12 treated knock‐in mice having a seizure compared to 8 out of 13 mice receiving the vehicle. Carbamazepine efficacy on seizures was progressive and correlated to an accumulation of carbamazepine‐epoxide in the brain. The cognitive abilities of treated knock‐in mice at 3 months of age were similar to those of wild‐t

Abstract Objective Carbamazepine is the first line treatment for patients affected by KCNQ2 developmental and epileptic encephalopathy. It is efficient to reduce or stop seizures in this context. However, its effect on the neurodevelopmental outcomes is debated. The aim of this study was to evaluate the efficacy of long‐term oral administration of carbamazepine in a mouse model of Kcnq2 dysfunction. Methods Mice were treated at weaning and during 70 days. The impact on seizures was measured, and blood samples were collected every week. At 3 months of age, all mice were tested using the Water T‐maze and Barnes maze tests to evaluate their cognitive abilities. Brain tissue was collected to measure carbamazepine and carbamazepine‐epoxide concentrations. Results After 70 days of carbamazepine treatment, the impact on seizures was strong in the Kcnq2 ‐DEE mice, with 1 out of 12 treated knock‐in mice having a seizure compared to 8 out of 13 mice receiving the vehicle. Carbamazepine efficacy on seizures was progressive and correlated to an accumulation of carbamazepine‐epoxide in the brain. The cognitive abilities of treated knock‐in mice at 3 months of age were similar to those of wild‐t

Lire l’article