TSHA-102 Produces Multidomain Functional Gains in Rett Syndrome

All 10 participants with Rett syndrome treated with a single intrathecal dose of TSHA-102 (Taysha Gene Therapies) gained or regained at least 1 developmental milestone in Part A of the phase 1/2 REVEAL trials.¹ Based on natural history data, these milestones carry a less than 6.7% likelihood of being achieved after age 6.¹ Elsa Rossignol, MD, MSc, of CHU Sainte-Justine, Université de Montréal, presented the data at the 2026 Child Neurology Society (CNS) Annual Meeting in Montréal, Canada.¹

TSHA-102 is an investigational adeno-associated virus (AAV) gene therapy delivered by lumbar intrathecal injection and designed to optimize MECP2 expression in the central nervous system.^1,3 No approved therapy for Rett syndrome targets its underlying genetic cause.¹ The presentation reflects a May 2025 data cutoff, the same cutoff behind topline Part A results Taysha announced before the FDA granted TSHA-102 breakthrough therapy designation in October 2025.²

What did REVEAL Part A show for TSHA-102 in Rett syndrome?

REVEAL Part A includes an adolescent and adult study (NCT05606614) and a pediatric study (NCT06152237).² Both are open-label, dose-escalation and dose-expansion studies enrolling patients with Rett syndrome due to MECP2 loss-of-function mutations.³

Participants aged 6 to 21 years received a single intrathecal dose of TSHA-102.¹ The low-dose cohort (n = 4) received 5.7 × 10¹⁴ vector genomes (vg), and the high-dose cohort (n = 6) received 1.0 × 10¹⁵ vg.¹ Multiple independent central raters assessed gain or regain of predefined developmental milestones using video evidence.¹

READ MORE: New Phase 1 Study Tests Intrathecal Gene Therapy Agent INS1201 in Duchenne Muscular Dystrophy

As of the May 2025 cutoff, participants achieved 22 developmental milestones plus 165 additional skills or improvements across core Rett syndrome domains.¹ Communication gains included use of phrases and improved communication, while fine motor gains included purposeful hand use and finger feeding.¹ Investigators also reported improved mobility in gross motor function, a domain in which the authors noted milestones are typically lost or missed after age 6.¹

TSHA-102 safety and autonomic outcomes in REVEAL Part A

Beyond motor and communication gains, investigators reported autonomic and other improvements, including absent or reduced breath holding and hyperventilation and reductions in seizures.¹ Both dose cohorts showed early improvements across multiple domains, which deepened over time contrary to natural history expectations, the authors wrote.¹ Initial low-dose data reported in June 2024 included improved breathing patterns in the first 2 adolescent and adult patients and a 25% reduction in seizure events at week 36 in 1 patient.³

TSHA-102 was well tolerated, with no treatment-related serious adverse events (SAEs) or dose-limiting toxicities (DLTs) as of the May 2025 cutoff.¹ The abstract did not report effect sizes or a concurrent control arm, and milestone gains were measured against natural history expectations rather than placebo.¹ The authors concluded the results support the disease-modifying potential of TSHA-102, with additional sub-analyses of neurological function planned for the presentation.¹

Taysha began dosing in the pivotal REVEAL Part B trial in the fourth quarter of 2025, evaluating a single 1 × 10¹⁵ vg dose in 15 female patients aged 6 to younger than 22 years.² The company has also aligned with the FDA on including safety data from its planned ASPIRE trial, in patients aged 2 to younger than 4 years, in a future biologics license application.² Abstract coauthors include Rumana Haque-Ahmed, chief regulatory officer of Taysha.^1,2

Taysha has estimated 15,000 to 20,000 patients are living with Rett syndrome across the United States, European Union, and United Kingdom.² The company expected to complete dosing across REVEAL and ASPIRE in the second quarter of 2026.² Part B uses the higher of the 2 Part A doses.^1,2

Click here for more CNS 2026 coverage.

References

1. Rossignol E, Berry-Kravis E, Haas R, et al. Multi-domain functional gains following TSHA-102 gene therapy across the Rett syndrome lifespan: safety and efficacy results from the REVEAL Part A phase 1/2 trial of TSHA-102 in pediatric and adolescent/adult cohorts. Presented at: 2026 Child Neurology Society Annual Meeting; October 14-17, 2026; Montréal, Canada. Abstract AOP-5.

2. Taysha doses first patient in pivotal trial for Rett syndrome gene therapy TSHA-102, aligns with FDA on BLA plans. NeurologyLive. January 30, 2026. https://www.neurologylive.com/view/taysha-doses-first-patient-pivotal-trial-rett-syndrome-gene-therapy-tsha-102-aligns-fda-bla-plans

3. Phase 1/2 studies highlight durable impacts of gene therapy TSHA-102 in Rett syndrome. NeurologyLive. June 18, 2024. https://www.neurologylive.com/view/phase-1-2-studies-highlight-durable-impacts-gene-therapy-tsha-102-in-rett-syndrome