All Rett patients in trial achieve motor milestones with gene therapy

Treatment with TSHA-102 drives lasting gains for women, girls in REVEAL

Written by Steve Bryson, PhD | June 24, 2026

All 12 girls and women with Rett syndrome given the gene therapy candidate TSHA-102 in a clinical trial gained or regained at least one developmental milestone within one year, with consistent responses seen across differing ages and disease severity levels, new trial data show.

Longer-term follow‑up data from Part A of the REVEAL Phase 1/2 clinical trial (NCT05606614) show a lasting, deepening treatment-related effect for all patients, according to researchers. Moreover, the team noted that additional improvements were seen beyond the 12-month mark, with functional gains continuing for the women and girls in the study — including among those with the longest follow-up at 30 months, or 2.5 years.

Improvements were seen in walking and speaking abilities, as well as in skills such as using utensils without assistance.

“The data demonstrated early, durable treatment effect across all 12 pediatric, adolescent and adult patients, with responses continuing to deepen over time,” Sean P. Nolan, chairman and CEO of Taysha Gene Therapies, the treatment’s developer, said in a company press release.

Meanwhile, Taysha has completed dosing in Part B — or the pivotal Phase 3 portion — of REVEAL, enrolling girls and women with Rett, ages 6-21. Six-month top-line data from this Phase 3 part, along with feedback from the U.S. Food and Drug Administration (FDA) toward the submission of an approval application, are expected early in 2027, according to the company.

“We believe the robust, clinically meaningful responses observed at both 6 and [12 months or more] post-treatment continue to demonstrate the potential for TSHA-102 to transform the treatment paradigm for this devastating disease,” Nolan said. “We plan to engage with the FDA to review the interim data and discuss next steps toward submitting the BLA [biologics license application], with topline results and regulatory feedback expected in the first half of 2027.”

FDA puts TSHA-102 gene therapy on fast track for Rett syndrome

Most cases of Rett, a rare neurodevelopmental disorder that primarily affects girls, are caused by mutations in the MECP2 gene, which plays an essential role in regulating brain cell function.

TSHA-102 is administered as a one-time treatment that delivers a functional copy of the MECP2 gene to cells in the nervous system. The therapy features a technology called miRARE, which helps manage MECP2 activity levels on a cell-by-cell basis to avoid toxic overactivity.

Early REVEAL data demonstrated TSHA-102’s safety

Interim data from Part A of REVEAL, along with results from a pediatric version (NCT06152237) of the trial with Rett girls, ages 5 to 8, showed that the gene therapy was generally safe and led to improvements in motor function, communication, and social skills.

The new Part A efficacy data, based on a May cutoff date, were from a dozen girls and women with Rett who were treated with a high or low dose of TSHA-102.

The data showed that all participants gained — or regained, for those who had lost skills — at least one developmental milestone by 12 months. These improvements spanned the core functional areas of fine motor skills, gross motor skills, and communication, and included meaningful speaking, eating, and walking gains.

The longer-term follow-up data showed that treatment effects were long-lasting and continued to deepen over time. Developmental milestone gains increased by 69% between six and 12 months, and by 94% between six months and the latest follow-up of 12 months or more, the data showed. Additionally, participants with the longest follow-up, at 30 months, continued to show functional gains.

In total, at a year or more post-treatment, 310 functional gains were observed across the 12 participants, averaging about 26 per patient. These comprised 31 developmental milestones and 279 additional skill gains and improvements. Responses were consistent regardless of age, disease severity, or the patients’ specific MECP2 mutations.

Improvements were also observed on several clinician-assessed outcome measures: the Revised Motor Behavior Assessment (R-MBA); the Clinician Global Impression-Improvement (CGI-I); and the Clinical Global Impression-Severity (CGI-S). This corroborated the functional gains reported.

TSHA-102 consistently drove early, durable functional gains across the core domains of the disease, including communicating with words or phrases, eating with utensils without assistance and walking with support, [with improvments continuing] to accumulate over time.

“Longer-term data from the REVEAL Phase 1/2 trials demonstrate remarkable responses following treatment with TSHA-102, far exceeding what would be expected based on the natural history of patients aged [6] years and older,” said Elsa Rossignol, MD, a professor at the Université de Montréal in Canada and a principal investigator in REVEAL. Rossignol noted that Rett patients older than 6 are considered the “developmental plateau population.”

“TSHA-102 consistently drove early, durable functional gains across the core domains of the disease, including communicating with words or phrases, eating with utensils without assistance and walking with support, which continue to accumulate over time,” Rossignol noted. “These outcomes support greater independence, reduce caregiver burden and enhance social engagement.”

As of a June data cutoff date, TSHA-102 was generally well tolerated across all 29 patients enrolled in the REVEAL Phase 1/2 and pivotal trials combined, with no treatment-related serious adverse events or dose-limiting toxicities reported, according to Taysha. All treatment-related adverse events were mild to moderate in severity, the developer noted.

Gene therapy ‘sponge’ revives healthy gene in Rett syndrome

Trial’s pivotal, Phase 3 portion now fully enrolled

Now, the REVEAL Phase 3 pivotal portion of the trial has completed recruitment, with enrollment of 17 girls and women with Rett. This study’s main goal is to determine the percentage of participants who gain or regain at least one of 28 natural history-defined developmental milestones. A response rate of 33% is the minimum threshold for success, the company noted.

In addition to the ongoing REVEAL trials, Taysha launched a Phase 3 trial called ASPIRE (NCT07480564) to evaluate TSHA-102 in four girls with Rett, ages 2 to 3. This trial is intended to support a broad treatment label covering patients ages 2 and older. A minimum of three months of ASPIRE safety data will be included in the planned BLA, per the developer.

“As we advance toward a potential BLA submission for TSHA-102, we remain committed to developing a comprehensive, scientifically rigorous data package informed by our ongoing discussions with the FDA,” Nolan said.

According to Rossignol, the current findings “[reinforce] the potential of TSHA-102 to deliver meaningful improvements for patients and families who continue to face profound unmet need.”

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Steve Bryson, PhD

About the Author

Steve holds a PhD in biochemistry from the Faculty of Medicine at the University of Toronto, Canada. As a medical scientist for 18 years, he worked in both academia and industry, where his research focused on the discovery of new vaccines and medicines to treat inflammatory disorders and infectious diseases. Steve is a published author in multiple peer-reviewed scientific journals and a patented inventor.