A Gene Therapy for Dravet Syndrome Cuts Seizures and Supports Development
Updated: 11 hours ago
On May 13, 2026, at the American Society of Gene & Cell Therapy (ASGCT) annual meeting in Boston, Encoded Therapeutics presented one-year results for ETX101, a one-time gene therapy for Dravet syndrome. The data were featured in the meeting's Presidential Symposium, a spotlight reserved for some of the year's most important work. At the highest dose tested, children had about a 76% median reduction in monthly seizures. Many also showed developmental gains, a first for this devastating form of childhood epilepsy.
Encoded announced that it has aligned with the FDA and started a pivotal study. In September, the company raised $275 million to carry ETX101 through that final stage.
Loss of inhibitory signaling
Dravet syndrome usually begins in the first year of life, often with long seizures triggered by fever. It progresses to frequent, drug-resistant seizures of many types. Children face developmental delays, movement and behavioral difficulties, and a high risk of sudden unexpected death in epilepsy (SUDEP).
Most cases are caused by a mutation in one copy of the SCN1A gene. SCN1A makes Nav1.1, a sodium channel that is especially important in inhibitory interneurons. These GABAergic neurons dampen activity in neural circuits. With only one working copy of SCN1A, interneuron firing is impaired, inhibition falls, and neural networks become hyperexcitable, which leads to seizures.
Current medicines can reduce seizures, but they rarely stop them, and they don't fix the underlying problem. Development often stalls even when seizures improve.
The clever part: turn up the gene that's already there
The obvious gene therapy fix would be to deliver a healthy copy of SCN1A. But there's a problem. The SCN1A gene is far too large to fit inside an AAV, the vector most often used to deliver genes to the brain.
Encoded's solution is a gene regulation approach. Instead of delivering the whole gene, ETX101 delivers a compact, engineered regulator. It boosts the activity of the patient's own healthy SCN1A copy. The working copy produces more Nav1.1, making up for the broken one.
Precision matters here. ETX101 is designed to act mainly in the inhibitory interneurons where Nav1.1 matters most. That targeting is built into the regulatory DNA carried by the vector.
The therapy uses AAV9 and is given as a single intracerebroventricular injection, directly into the fluid-filled spaces of the brain. It's designed to work for the long term after one dose.
What the data showed
The results come from Encoded's POLARIS program, three open-label, dose-escalation trials in children aged 6 months to 7 years with SCN1A-positive Dravet syndrome. The findings Encoded reported:
Seizures: Over 52 weeks, ETX101 reduced seizures in a dose-dependent way. At dose level 3, the median reduction in monthly countable seizures was about 76%. The company stressed that this came "during a developmental window typically associated with increasing seizure burden," when seizures usually get worse despite standard medicines.
Development: Children who reached 52 weeks showed improvements in adaptive behavior on the Vineland scales, with notable gains in communication and motor skills.
Treating early: Children treated before age 2 showed cognitive trajectories "generally consistent with neurotypical development" during the observation period. That's a sharp contrast to the stalling usually seen in Dravet.
Safety: There were no treatment-related serious adverse events across four dose levels. Liver enzyme elevations, a known effect of AAV therapies, caused no symptoms and resolved in all participants.
The usual cautions apply. The top-dose group included only three children, and these were open-label trials without a placebo group. The pivotal study is designed to confirm the effect in a larger, more rigorous setting.
Why this matters
It targets the cause, not the symptoms. Nearly every existing Dravet treatment tries to calm seizures. ETX101 is designed to restore Nav1.1 levels in the inhibitory interneurons that need it.
It suggests timing is everything. If children treated before age 2 really do stay on a typical developmental path, early diagnosis becomes critical. That could strengthen the case for genetic testing soon after a baby's first unusual seizure.
It opens a new playbook. Many brain disorders are caused by having only one working copy of a gene, a situation called haploinsufficiency. Many of those genes are, like SCN1A, too big for AAV. Boosting the healthy copy with a small regulator could be a template for other conditions. Encoded is also developing an approach for Angelman syndrome.
The bottom line
ETX101 doesn't replace a broken gene. It turns up the good one. One year in, children in the trial are having far fewer seizures, and the youngest are developing in ways doctors rarely see in Dravet syndrome. With a pivotal study now running and new funding secured, this is one of the most hopeful stories in neurological gene therapy this year.
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— T.N., Gene Tech Times
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