Fit for purpose application of currently existing animal models in the discovery of novel epilepsy therapies

Animal seizure and epilepsy models continue to play an important role in the early discovery of new therapies for the symptomatic treatment of epilepsy. Since 1937, with the discovery of phenytoin, almost all anti-seizure drugs (ASDs) have been identified by their effects in animal models, and millions of patients world-wide have benefited from the successful translation of animal data into the clinic. However, several unmet clinical needs remain, including resistance to ASDs in about 30% of patients with epilepsy, adverse effects of ASDs that can reduce quality of life, and the lack of treatments that can prevent development of epilepsy in patients at risk following brain injury. The aim of this review is to critically discuss the translational value of currently used animal models of seizures and epilepsy, particularly what animal models can tell us about epilepsy therapies in patients and which limitations exist. Principles of translational medicine will be used for this discussion. An essential requirement for translational medicine to improve success in drug development is the availability of animal models with high predictive validity for a therapeutic drug response. For this requirement, the model, by definition, does not need to be a perfect replication of the clinical condition, but it is important that the validation provided for a given model is fit for purpose. The present review should guide researchers in both academia and industry what can and cannot be expected from animal models in preclinical development of epilepsy therapies, which models are best suited for which purpose, and for which aspects suitable models are as yet not available. Overall further development is needed to improve and validate animal models for the diverse areas in epilepsy research where suitable fit for purpose models are urgently needed in the search for more effective treatments.