Epilepsy in Dravet Syndrome—Current and Future Therapeutic Opportunities

Abstract

Dravet Syndrome (DS) is a developmental epileptic encephalopathy characterized by drug-resistant seizures and other clinical features, including intellectual disability and behavioral, sleep, and gait problems. The pathogenesis is strongly connected to voltage-gated sodium channel dysfunction. The current consensus of seizure management in DS consists of a combination of conventional and recently approved drugs such as stiripentol, cannabidiol, and fenfluramine. Despite promising results in randomized clinical trials and extension studies, the prognosis of the developmental outcomes of patients with DS remains unfavorable. The article summarizes recent changes in the therapeutic approach to DS and discusses ongoing clinical research directions. Serotonergic agents under investigation show promising results and may replace less DS-specific medicines. The use of antisense nucleotides and gene therapy is focused not only on symptom relief but primarily addresses the underlying cause of the syndrome. Novel compounds, after expected safe and successful implementation in clinical practice, will open a new era for patients with DS. The main goal of causative treatment is to modify the natural course of the disease and provide the best neurodevelopmental outcome with minimum neurological deficit.

Reintroducing Fenfluramine as a Treatment for Seizures: Current Knowledge, Recommendations and Gaps in Understanding

“…Recently, the anti-obesity medication fenfluramine (FFA) has been successfully repurposed, and regulatory agencies have approved its use for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome. 3 , 4 This narrative review aims to provide a comprehensive analysis of fenfluramine’s mechanism of action as an antiseizure medication, its clinical pharmacology, and relevant clinical studies. Special emphasis is placed on evaluating its efficacy in reducing seizures and examining potential adverse effects.…”