Uncovering targets and molecular pathways for personalizing treatment in epilepsy

Despite licensing many new antiseizure drugs over the last few decades, the proportion of pharmacoresistant epileptic seizures has remained largely unchanged at about 30%. However, recent progress in genetics has revealed new and more specific therapeutic targets that can be addressed through improved drug design and advancements in gene therapy, such as improved antisense oligonucleotide chemistry. Furthermore, many of these developing new precision therapies hold the promise of shifting from purely symptomatic toward disease-modifying treatment, particularly in the field of developmental and epileptic encephalopathies.

This article focuses on novel potential therapeutic targets, including those encoded by causative genes for epileptic syndromes and those that show promise for favorably impacting common epilepsies or epileptogenesis. The covered areas are organized according to different molecular protein targets.

Therapy in the near future will likely be based predominantly on specific small molecules or gene therapies, such as antisense oligonucleotides. Among currently used allele-specific therapeutic designs, only some loss- or gain-of-function pathological variants are expected to profit from them. Allele-specific gene therapy may be a promising treatment for those diseases that would not benefit from currently used allele-nonspecific designs.