RNA therapeutics for epilepsy: an emerging modality for drug discovery.

Abstract

Drug discovery in epilepsy began with the finding of potassium bromide by Sir Charles Locock in 1857. The following century witnessed the introduction of phenotypic screening tests for discovering antiseizure medications (ASMs). Despite the high success rate of developing ASMs, they have so far failed in eliminating drug-resistance and in delivering disease-modifying treatments. This emphasises the need for new drug discovery strategies in epilepsy. RNA-based drugs have recently shown promise as a new modality with the potential of providing disease-modification and counteracting drug-resistance in epilepsy. RNA therapeutics can either be directed toward non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), or towards messenger RNAs (mRNAs). The former show promise in sporadic, non-genetic epilepsies as interference with ncRNAs allow for modulation of entire disease pathways, while the latter seems more promising in monogenic childhood epilepsies. Here, we describe therapeutic strategies for modulating disease-associated RNA molecules and highlight the potential of RNA therapeutics for the treatment of different patient populations such as sporadic, drug-resistant epilepsy, and childhood monogenic epilepsies.