Investigational new drugs for the treatment of Dravet syndrome: an update

ABSTRACT

Introduction

While there are already approved anticonvulsants for treatment of children with Dravet syndrome, disease modifying therapy is at its beginning.

Areas covered

This narrative review is updating the latest information about efficacy and safety of both anticonvulsant and disease modifying investigational drugs for Dravet syndrome. Relevant publications were searched for in MEDLINE, GOOGLE SCHOLAR, SCINDEKS, and CLINICALTRIALS.GOV databases, from the dates of their foundation till January 2023.

Expert opinion

The main advancements were made in the treatment of Dravet syndrome with confirmed haploinsufficiency of SCN1A gene. The application of antisense oligonucleotides has so far proven to be the most successful within disease-modifying therapy, but it also requires further refinement of the methodology of application and delivery to target cells, as well as additional testing of the effectiveness of antisense oligonucleotides outside of TANGO technology. Also, the full potential of gene therapy has yet to be explored, given that high capacity adenoviral vectors that can incorporate the SCN1A gene have recently been prepared.

KEYWORDS:

• Causal therapy
• Dravet syndrome
• investigational drugs
• oligonucleotides

Article highlights

• After approval of fenfluramine for treatment of Dravet syndrome a number of second-generation serotonergic drugs (lorcaserin, clemizole, trazodone, and LP352) are currently tested in clinical trials

• There are promising interim results of clinical trials with antisense oligonucleotide STK-001, which probably will become the first disease-modifying therapy of Dravet syndrome with marketing authorization

• The only gene therapy that reached clinical trial phase is ETX101, which contains a gene for a transcription factor that specifically promotes expression of the functional allele of the SCN1A gene

This box summarizes key points contained in the article.

Declaration of interest

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.

Additional information

Funding

The article was partially funded by the Ministry of Education, Science and Technological Development of the Republic of Serbia, through grant No 175007.