Antiepileptogenesis and disease modifying therapy

Epilepsy the most common, serious chronic neurological disease worldwide, affecting >۵۰ million people globally. Despite many new anti-seizure medications drugs (ASMs) being introduced into practice over the past ۲۰ years, the treatment outcomes remain unsatisfactory for many patients. Current treatment with ASMs is symptomatic, suppressing seizures but not having sustained effects, and no effects on the accompanying comorbidities. There has been little reduction in the proportion of patients who are refractory to medical treatment, with approximately one third continuing to have seizures despite trials of treatment with multiple different AEDs. There is no medical treatment that has been demonstrated to be effective at preventing the development of epilepsy after an epileptogenic insult, to prevent progression of the epilepsy or its comorbidities, or to mitigate or cure the condition. A major challenge for translational researchers is to discover and develop new treatments that address these major treatment gaps, in particular to develop treatments that can prevent or mitigate the development of epilepsy (i.e. anti-epileptogenic), mitigate its severity (including ASM resistance), or even cure the epilepsy. Advances in the understanding of the fundamental neurobiology of seizures and epileptogenesis have suggested new targeted approaches by which this may be achieved. Rigorous evaluation of these with studies using clinically relevant “true epilepsy” models is essential to provide the evidence base to select the most promising novel treatments to translate into clinical trials, and then to ultimately improve outcomes for patients with this disabling condition.