Rett gene therapy drives lasting developmental gains: Long-term data
They deepened over time across gross motor function, communication
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All 10 patients with Rett syndrome treated with Neurogene‘s gene therapy NGN-401 continued to make developmental gains over 2.5 years of follow-up, with no plateau or loss of skills observed, according to long-term data from a Phase 1/2 clinical trial.
The data showed that these gains deepened over time and were seen across hand function, gross motor function, and communication. The company also noted that milestones progressed in a stepwise, developmentally ordered sequence, meaning skills built on one another over time rather than appearing in isolation.
“We are encouraged by the long-term Phase 1/2 data across a broad age range and wide spectrum of disease severity, which we believe demonstrate that NGN-401 is driving gain of durable and clinically meaningful developmental milestones,” Rachel McMinn, PhD, founder and CEO of Neurogene, said in a company press release. “Importantly, the gains of developmental milestones are not isolated events — they build over time with participants acquiring multiple milestones across the core Rett syndrome functional domains of hand function, gross motor function and communication.”
Meanwhile, dosing is complete in the Phase 3 Embolden clinical trial (NCT05898620), which is testing NGN-401 in up to 33 female Rett patients, ages 3 and older. That trial is designed to serve as a basis for applications seeking approval of the gene therapy, with top-line data anticipated by the second half of 2027.
NGN-401 designed to deliver healthy version of key gene to brain cells
A rare neurological disorder, Rett syndrome, which affects mostly girls and women, is caused primarily by mutations in the MECP2 gene. Such defects lead to low levels of MeCP2, a protein essential for normal brain development and communication between nerve cells.
NGN-401 is designed to deliver a healthy version of the gene to brain cells, restoring MeCP2 protein production. It’s administered via intracerebroventricular infusion, meaning it is injected directly into the brain’s fluid-filled spaces. NGN-401 also incorporates Neurogene’s EXACT technology, which tightly regulates MeCP2 protein levels on a cell-by-cell basis.
Interim data reported last year showed that NGN-401 had a generally favorable safety profile, with no serious side effects. Among eight girls who received treatment with NGN-401 between the ages of 4 and 10, functional gains were seen across a spectrum of disease severity.
As of a data cutoff on June 16, 2026, representing a 12- to 30-month post-treatment follow-up, all 10 participants treated in the trial had achieved at least one developmental milestone. They also showed improvement on the Clinical Global Impression-Improvement scale, a standard measure clinicians use to rate overall change in a patient’s condition.
This multidomain progression is not observed in the natural history of Rett syndrome, and we believe supports NGN-401’s differentiated profile, driven by its purposeful design and targeted delivery.
In total, 47 developmental milestones were gained, an average of 4.7 per participant. All participants gained at least one milestone within the past 12 months, and seven of the 10 gained two or more milestones, demonstrating improvement in at least two of the core areas affected by Rett syndrome.
Neurogene reported that these gains have not leveled off or reversed, with continued, progressive improvement through 30 months and no milestones lost.
The gene therapy also showed a rapid onset of effect, with a median time to first clinical improvement of two months after dosing. Milestone gains deepened as follow-up continued, increasing by 95% between six and 12 months and by 147% between six months and 12 months or later.
Participants also showed clinically meaningful improvement on two other validated measures, the Rett Syndrome Gross Motor Scale and the Rett Syndrome Hand Function Scale, according to the company.
“This multidomain progression is not observed in the natural history of Rett syndrome, and we believe supports NGN-401’s differentiated profile, driven by its purposeful design and targeted delivery,” McMinn noted.
Findings consistent with a restart of developmental progression
On safety, Neurogene reported that NGN-401 remains generally well tolerated among the 35 participants dosed to date, including those in the ongoing Phase 3 Embolden trial.
All treatment-related side effects have been mild or moderate, and most are known potential risks associated with gene therapies delivered by an adeno-associated virus vector that have resolved or are resolving. No new treatment-related serious adverse events have been reported since the prior data cutoff in October 2025.
Bernhard Suter, MD, medical director of the Blue Bird Circle Rett Center at Texas Children’s Hospital and a principal investigator on the trial, described the findings as consistent with a restart of developmental progression.
“In typical development, children gain milestones in an organized, cumulative sequence, with each milestone building on the last; in Rett syndrome, that process is stopped by regression,” he said, adding that participants are now “gaining greater independence and are more engaged in day-to-day activities with their families.”
The new data were presented alongside a poster on the Rett Syndrome Natural History Study at the 2026 International Rett Syndrome Foundation Scientific Meeting, recently held in Prior Lake, Minnesota.
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