Introduction: Antiseizure medications are the mainstay of
epilepsy treatment. Currently
therapies are not specific to
epilepsy etiology, and control
seizures in two-thirds of cases. Drugs in clinical development aim to bridge that gap by targeting novel receptors and epileptogenesis. While currently approved antiseizure medications target focal or
generalized epilepsies regardless of etiology, newly approved and investigational
epilepsy drugs also target rare or orphan
epilepsy syndrome indications, such as Lennox-Gastaut or
Dravet syndrome. We identified
investigational drugs through the
Epilepsy Foundation pipeline tracker and conference proceedings of recent novel
epilepsy drug conferences (XV AEDD, XIV EILAT).Areas covered: We review antiseizure medications in clinical development and their targets (
GABA,
T-type calcium channels, 5-HT,
potassium channels). We also discuss drugs with unknown or multiple mechanisms of action (
cannabinoids,
carisbamate,
cenobamate).
Therapies with potential disease-modifying effects in preclinical and clinical development are then outlined, ranging from gene-targeted treatments (
antisense oligonucleotide, gene therapy, antisense transcript regulators) targeting specific genetic
epilepsies,
mTOR inhibitors, to
inflammation-targeted treatments.Expert opinion: Drugs to treat novel targets to control
seizures as well as prevent epileptogenesis offer great promise. To assess disease modifying agents, we may need new clinical trial designs.
Precision medicine therapies for genetic
epilepsies may control
seizures and restore brain health.