Novel epilepsy treatments in clinical development

Despite the introduction of many novel antiseizure medications (ASMs), about one third of people with epilepsy remain resistant to the pharmacotherapy. Currently available ASMs have other limitations, including a significant burden of adverse effects and the fact that their action on seizures is purely symptomatic and has no impact on the underlying disease. To address these shortcomings, intensive research is ongoing to develop newer treatments with improved effectiveness. This article provides a narrative review of epilepsy treatments currently in clinical development, grouped into three categories (i) novel small-molecule chemical entities; (iii) gene-targeted therapies, including antisense oligonucleotides, vector gene therapies and cell-based therapies; (iii) therapeutic devices. As an indication of ongoing trends in epilepsy drug development, many of these investigational treatments are directed at rare syndromes. Some of these treatments also target the underlying etiology, with the potential to modify the trajectory of the disease and to impact favorably on neurodevelopment and epilepsy comorbidities. For some treatments discussed in this review, promising preliminary efficacy data are already available, offering hope for millions of people with epilepsy who do not adequately respond to currently available therapies.