Webpage https://episafe.
Research grant PCE nr 39/2022
Project ID PN-III-P4-PCE-2021-1422
Title Drug safety profiles of two newly-aproved antiepileptics by in vitro screening for pro-arrhythmogenic risk and BBB drug transport
Acronyme Episafe
Budget 1.200.000 lei / ~ 250.000 euro
Period 01.06.2022 – 31.12.2024
Principal investigator Prof Dr Beatrice Mihaela RADU
Abstract
Epilepsy is a widespread medical condition and according to the World Health Organisation is among the most common neurological disorders. Drug resistance is a major challenge for 30% of the epileptic patients that fail to respond to any medication. Any drug must meet the safety standards and in the respect, newly-aproved or older antiepileptic medications must be evaluated for pro-arrhythmogenic risk and blood brain barrier (BBB) drug transport/permeability. The goal of this project is to analyze the in vitro drug safety profiles of two newly-aproved antiepileptics, cenobamate and fenfluramine, using cell lines expressing human cardiac ion channels, human microvascular endothelial cells and commercial/patient human induced pluripotent stem cells (hiPSCs) derived cells. The pro-arrhythmogenic risk will be assessed by an original patented method using patch-clamp recordings of at least five ion currents and of externally paced action potentials. The drug pharmacokinetics at the BBB level will be investigated by measuring: i) drug permeability based on transendothelial electrical measurements in mono- and co-cultures conditions, (ii) eflux pumps expression by Western blot, immunofluorescence and qRT-PCR, and (iii) calcium signaling changes by ratiometric measurements. The expected results of this project will have a major impact in the pharmaceutical research/industry and personalised medicine.