Limitations of animal epilepsy research models: Can epileptic human tissue provide translational benefit?

Abstract

Advancement of understanding the etiology and treatment of epilepsy has largely depended on the use of acute and chronic animal models. An alternative approach, which is being increasingly used by a select number of laboratories worldwide, is to perform functional mechanistic studies in brain slices of living human tissue resected during surgery for drug resistant epilepsies. Pharmacoresistant epilepsy is a major clinical problem with a significant proportion of patients not receiving any symptomatic benefit from available anti-epileptic drugs. Animal models of epilepsy have dominated the landscape with regard to research and development, however they have failed to deliver new agents that would provide seizure control in patients with drug refractory epilepsy. Moreover, these models have considerable issues with respect to validity and animal welfare considerations. A compelling alternative is the use of live human epileptic tissue, which recapitulates a number of key features of refractory epilepsy. The use of live epileptic human tissue offers unprece­dented opportunities to understand the mechanisms associated with difficult to treat epilepsy whilst also permitting studies of efficacy of novel agents that are being developed to alleviate epilepsy in drug resistant patients.