Pharmacogenetics of Drug-Resistant Epilepsy (Review of Literature)

Abstract

Pharmacogenomic studies in epilepsy are justified by the high prevalence rate of this disease and the high cost of its treatment, frequent drug resistance, different response to the drug, the possibility of using reliable methods to assess the control of seizures and side effects of antiepileptic drugs. Candidate genes encode proteins involved in pharmacokinetic processes (drug transporters, metabolizing enzymes), pharmacodynamic processes (receptors, ion channels, enzymes, regulatory proteins, secondary messengers) and drug hypersensitivity (immune factors). This article provides an overview of the literature on the influence of genetic factors on treatment in epilepsy.

GABAA Receptor Variants in Epilepsy

“…Given the progress of genetic sequencing capacity, genetic screening would provide valuable information for effective treatment plan. Over 30% of epilepsy patients are resistant to conventional anti-epilepsy drug treatment partially because current treatments focus on relieving symptoms instead of targeting causative factors (100). Therefore, novel therapeutic strategy is urgently needed with the consideration of the underlying disease-causing mechanism.…”

The endoplasmic reticulum membrane complex promotes proteostasis of GABAA receptors

“…Recent advance in genetics has identified over 150 epilepsy-associated variants in the major subunits (a1, b2, b3, and g2) of GABA A receptors (Absalom et al, 2022;Fu et al, 2022;Hernandez and Macdonald, 2019;Hirose, 2014). Despite the development of numerous anti-seizure drugs, about one-third epilepsy patients are resistant to current drug treatment (Rincon et al, 2021), and many of them have genetic causes (Smolarz et al, 2021). Therefore, there is an urgent need to develop new therapeutic strategy to treat epilepsy, especially drug-resistant epilepsy.…”

The Endoplasmic Reticulum Membrane Complex Promotes Proteostasis of GABAAReceptors

“…Recent advance in genetics has identified over 150 epilepsy-associated variants in the major subunits (α1, β2, β3, and γ2) of GABAA receptors (Fu et al, 2022;Hernandez and Macdonald, 2019;Hirose, 2014). Despite the development of numerous anti-seizure drugs, about one third epilepsy patients are resistant to current drug treatment (Rincon et al, 2021), and many of them have genetic causes (Smolarz et al, 2021). Therefore, there is an urgent need to develop new therapeutic strategy to treat epilepsy, especially drug-resistant epilepsy.…”