Current and promising therapeutic options for Dravet syndrome

ABSTRACT

Introduction

Dravet Syndrome (DS) is a developmental and epileptic encephalopathy carrying high-level psychobehavioral burdens. Although the disease has been known for almost 4 decades, and despite significant progress in the understanding of its physiopathology and natural course, the pharmacological treatment leaves patients and caregivers with significant unmet needs. This review provides a summary of the current and promising therapeutic options for DS

Areas covered

PubMed and ClinicalTrials.gov were screened using ‘Dravet Syndrome’ OR ‘DS,’ AND ‘pharmacotherapy,’ AND ‘treatments.’ Randomized clinical trials, structured reviews, and meta-analyses were selected for in-human application of well-known anti-seizure medications; while in-vivo experiments on models of DS were selected to evaluate the potential of new therapeutic strategies.

Expert opinion

The search for new pharmacological treatment options is led by the need for care and defeat of the natural course of the disease, an aspect still largely neglected by the available therapeutic strategies. Yet, the last 6 years have led to a climate of increased interest and availability of clinical trials. Particularly, gene therapy could hopefully prevent DS evolution by directly relieving the specific genetic defect, although the possibility of off-target editing, and the uneasy administration route have still largely prevented its use.

KEYWORDS:

• Dravet syndrome
• epilepsy
• pharmacotherapy
• gene editing

Article highlights

• Dravet syndrome (DS) is a developmental and epileptic encephalopathy carrying high-level treatment challenges.

• The unmet needs for both patients and their caregivers remain significant.

• Recently, new drugs have been added to the therapeutic algorithm for DS (i.e. cannabidiol and fenfluramine).

• Soticlestat, clemizole, lorcaserin, acetylcholinesterase inhibitors, and ataluren are emerging as additional therapeutic possibilities.

• Great expectations deal in gene editing-based therapies.

Acknowledgments

This work was developed within the framework of the DINOGMI Department of Excellence of MIUR 2018–2022 (legge 232 del 2016).

Declaration of interest

A Riva has received honoraria from Kolfarma s.r.l, Proveca Pharma Ltd, and PTC Therapeutics. P Striano has served on a scientific advisory board for the Italian Agency of the Drug (AIFA); has received honoraria from GW pharma, Kolfarma s.r.l., Proveca Pharma Ltd, and Eisai Inc.; and has received research support from the Italian Ministry of Health and Fondazione San Paolo. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

AR: study design, literature search, and wrote the manuscript. GD: literature search and wrote the manuscript. DT: wrote the manuscript. EA, GB, VI, MSV, and AV: critical revision of the manuscript. PS: study design and supervision. All authors contributed to the article and approved the submitted version.

Additional information

Funding

This paper was not funded.