Seizure-suppressor genes: can they help spearhead the discovery of novel therapeutic targets for epilepsy?

Introduction: Epilepsies are disorders of neuronal excitability characterized by spontaneously recurrent focal and generalized seizures, some of which result from genetic mutations. Despite the availability of antiseizure medications, pharmaco-resistant epilepsy is seen in about 23% of epileptic patients worldwide. Therefore, there is an urgent need to develop novel therapeutic strategies for epilepsies. Several epilepsy-associated genes have been found in humans. Seizure susceptibility can also be induced in Drosophila mutants, some showing features resembling human epilepsies. Interestingly, several second-site mutation gene products have been found to suppress seizure susceptibility in the seizure genetic model Drosophila. Thus, these so-called 'seizure-suppressor' gene variants may lead to developing a novel class of antiseizure medications.

Area covered: This review evaluates the potential therapeutic of seizure-suppressor gene variants.

Expert opinion: Studies on epilepsy-associated genes have allowed analyses of mutations linked to human epilepsy by reproducing these mutations in Drosophila using reverse genetics to generate potential antiseizure therapeutics. As a result, about fifteen seizure-suppressor gene mutants have been identified. Furthermore, some of these epilepsy gene mutations affect ligand-and voltage-gated ion channels. Therefore, a better understanding of the antiseizure activity of seizure-suppressor genes is essential in advancing gene therapy and precision medicine for epilepsy.