The Changing Landscape of Dravet Syndrome

Veronica Hood, PhD

(Credit: Dravet Syndrome Foundation)

The First Spark: Identifying Dravet Syndrome

Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy (DEE) that was first described in 1978 by French neurologist Charlotte Dravet ,MD.¹ Originally termed severe myoclonic epilepsy of infancy, (SMEI), the name was later updated to reflect the lifelong impact and broader range of seizure types.^2,3

Patients were identified based on clinical symptoms—most notably the characteristic onset of prolonged, often febrile, treatment-resistant seizures in otherwise healthy infants. With age, developmental challenges emerge, impacting speech, cognition, motor function, and behavior.⁴ Patients may also experience autonomic dysfunction, sleep disturbances, and worsening gait.⁵ DS also carries a high risk of premature mortality, up to 20%, most often because of sudden unexpected death in epilepsy (SUDEP).^2,6 Notably, anti-seizure medications classified as sodium channel blockers, such as lamotrigine, often worsened seizures for patients with DS.

Kindling Progress: Building Research and Community

In 2001, researchers discovered the majority of patients with DS carry loss-of-function variants in one copy of the SCN1A gene, which encodes a sodium channel critical for brain function.⁸ This discovery enabled confirmatory genetic testing to aid in the clinical diagnosis, and opened the door to research aimed at precision medicine. However, nearly a decade later little had changed in the landscape for patient families: no new therapies were in development, diagnoses were still delayed despite the advancements in genetic testing, and research funding was minimal. In 2009, families came together to establish the Dravet Syndrome Foundation (DSF) with a primary mission to fund and advocate for research.⁹

Over the following decade, a collaborative community of patient-families, scientists, health care providers, and pharmaceutical innovators began to change the landscape. Scientific discoveries uncovered the molecular and cellular impacts of SCN1A haploinsufficiency and expanded our understanding of the clinical spectrum of symptoms. Between 2018 and 2020, 3 antiseizure medications received FDA-approval for use in DS: stiripentol (Diacomit; Biocodex),¹⁰ pharmaceutical-grade cannabidiol (Epidiolex;Jazz Pharmaceuticals),¹¹ and fenfluramine (Fintepla; UCB).¹² The development of expert consensus guidelines followed to support diagnosis and evidence-based treatment decisions.¹³

In 2022, the patient community organized an Externally-Led Patient Focused Drug Development Meeting, detailing the lived-experience of navigating DS to the FDA; this meeting highlighted that despite new therapies, patients continue to experience refractory seizures and have few treatment options for non-seizure symptoms.⁹

Wired for Precision: A New Era in the Treatment of Dravet Syndrome

The momentum in the research space has laid the foundation for a more transformative era as precision medicine becomes a reality. Leveraging the advancements in genetics, molecular biology, and delivery technology, scientists are developing treatments aimed at the underlying haploinsufficiency of SCN1A with the hope to effectively treat seizures as well as the other symptoms of DS and truly modify the entire course of the disease.

The most advanced of these novel therapies, an antisense oligonucleotide (ASO) called zorevunersen (Stoke Therapeutics), is designed to boost SCN1A expression by modifying RNA-splicing.¹⁴ Completion of 2 phase 1/2 studies signaled a favorable safety profile and early signs of seizure reduction and developmental gains, providing the first signal of disease modification in DS.¹⁵ A pivotal, international phase 3 study (NCT06872125) of zorevunersen began enrollment in 2025.

Another approach, ETX101 (Encoded Therapeutics), uses an adeno-associated viral (AAV) vector to deliver an engineered transcription factor that upregulates SCN1A expression.¹⁶ This gene therapy is currently in a phase 1/2 clinical study (NCT05419492).¹⁶

Several other genetic-based therapies are in preclinical development and showing strong potential in animal models of DS.^17,18 At the same time, the community is working to ensure equitable access to genetic testing, clinical trials, and future therapies. Decades of advocacy and scientific progress have brought us to the threshold of personalized, disease-modifying treatments—and a new chapter in the DS story.

REFERENCES
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11. Devinsky O, Cross JH, Laux L, et al. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017;376(21):2011-2020. doi:10.1056/NEJMoa1611618
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14. Han Z, Chen C, Christiansen A, et al. Antisense oligonucleotides increase Scn1a expression and reduce seizures and SUDEP incidence in a mouse model of Dravet syndrome. Sci Transl Med. 2020;12(558):eaaz6100. doi:10.1126/scitranslmed.aaz6100
15. Laux et al (2024) Zorevunersen (STK-001) Demonstrates Potential for Disease Modification Including Reductions in Seizures and Improvements in Cognition and Behavior in Children and Adolescents with Dravet Syndrome (DS). AES Annual Meeting Abstract # 2.379. Accessed June 22, 2025. https://aesnet.org/abstractslisting/zorevunersen-stk-001-demonstrates-potential-for-disease-modification-including-reductions-in-seizures-and-improvements-in-cognition-and-behavior-in-children-and-adolescents-with-dravet-syndrome-ds
16. Tanenhaus A, Stowe T, Young A, et al. Cell-Selective Adeno-Associated Virus-Mediated SCN1A Gene Regulation Therapy Rescues Mortality and Seizure Phenotypes in a Dravet Syndrome Mouse Model and Is Well Tolerated in Nonhuman Primates. Hum Gene Ther. 2022;33(11-12):579-597. doi:10.1089/hum.2022.037
17. Fadila S, Beucher B, Dopeso-Reyes IG, et al. Viral vector-mediated expression of NaV1.1, after seizure onset, reduces epilepsy in mice with Dravet syndrome. J Clin Invest. 2023;133(12):e159316. Published 2023 Jun 15. doi:10.1172/JCI159316
18. Mich JK, Ryu J, Wei AD, et al. Interneuron-specific dual-AAV SCN1A gene replacement corrects epileptic phenotypes in mouse models of Dravet syndrome. Sci Transl Med. 2025;17(790):eadn5603. doi:10.1126/scitranslmed.adn5603