The genetics of pharmacoresistance in mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy in adults. Many anti-seizure medications (ASMs) are available for treating patients with epilepsy. However, even with optimal clinical treatment, at least one-third of patients with MTLE will be pharmacoresistant. Pharmacoresistance to ASM is likely a multifactorial condition involving genetic and environmental factors. In recent years, the increased knowledge generated by genetic discoveries provided powerful tools to study the contribution of genetics to disease and response to treatment in many disorders. The genetic aspects influencing pharmacoresistance to ASMs are thought to affect the classic mechanisms in pharmacology, such as pharmacokinetics and pharmacodynamics. In this lecture, I will present and discuss the contribution of genetic factors to understanding the basic mechanisms determining pharmacoresistance in patients with MTLE. Furthermore, I intend to provide an overview and a critical discussion of the findings, limitations, new approaches, and future directions of these studies aiming to improve the treatment of patients with pharmacoresistant MTLE