On the Development of New Drugs for the Treatment of Drug-Resistant Epilepsy: An Update on Different Approaches to Different Hypotheses

ALAN TALEVI

Pharmacoresistance in Epilepsy From Genes and Molecules to Promising Therapies 2nd Edition

Springer

Año: 2023; p. 429 - 451

Home Pharmacoresistance in Epilepsy ChapterOn the Development of New Drugs for the Treatment of Drug-Resistant Epilepsy: An Update on Different Approaches to Different HypothesesAlan Talevi ChapterFirst Online: 30 August 2023AbstractDespite the continuous expansion of the available pharmacological options for the treatment of epilepsies and remarkable advances in understanding their pathophysiology, the proportion of refractory patients has remained roughly unchanged over the past 100 years.In the last decade, hypotheses that try to explain the drug-resistant phenotype have increased in number and their scope has been more precisely specified, and some major advances related to some of these hypotheses have been realized, both at the preclinical and clinical levels. These include the use of gene therapies to revert the pharmacoresistant phenotype in animal models of epilepsy, advance into clinical trials and approval of tailored multitarget therapeutics (e.g., padsevonil and cenobamate) exhibiting encouraging results on refractory patients, approval of new drugs with new (and sometimes complex) mechanisms to address particularly severe and difficult-to-treat epileptic syndromes, and the first reports of applications of network analysis to rationally select combinations of antiseizure medications. The introduction of the Epilepsy Therapy Screening Program also constitutes a significant milepost that will possibly have a major impact on the development of new, more efficacious therapeutic options against epilepsy, as the focus of the international guidelines to screen for novel medications against epilepsy is now on refractory epilepsy and disease-modifying interventions.This chapter, which intends to be a critical update of the one published back in the first edition of this volume, overviews the current hypotheses that intend to explain refractory epilepsy as well as plausible therapeutic strategies to address some of them.