1st child dosed with gene therapy TSHA-102 in REVEAL trial

Study will initially test 2 doses in 6 children to determine optimum dosage

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The first girl with Rett syndrome has been given the experimental gene therapy TSHA-102 in a clinical trial, according to the treatment’s developer, Taysha Gene Therapies.

“Dosing the first pediatric patient with Rett syndrome marks an important step forward in our efforts to broaden the clinical evaluation of TSHA-102 to younger patients with earlier stages of Rett syndrome,” Sukumar Nagendran, MD, Taysha’s president and head of research and development, said in a company press release. “We are pleased with our progress on expanding the study of TSHA-102 across a broad population of ages and stages of Rett syndrome to bring a potentially transformative treatment option to all patients and families suffering from this devastating disease.”

Rett syndrome is mainly caused by mutations in the MECP2 gene. TSHA-102 aims to deliver a shortened but functional version of this gene to nerve cells, along with regulatory components to prevent toxicity from too-high activity of the therapeutic gene. The gene therapy is given by injection into the spinal cord (intrathecal injection).

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Phase 1/2 trial of Rett syndrome gene therapy to dose 3rd patient

Phase 1/2 REVEAL trial testing TSHA-102 in girls with Rett syndrome stage 3

“Designed as a one-time, disease-modifying treatment with the ability to mediate MECP2 expression [activity] on a cell-by-cell basis, TSHA-102 holds the potential to address a significant unmet medical need for the Rett syndrome community,” said Elizabeth Berry-Kravis, MD, PhD, a professor at Rush University Medical Center.

The Phase 1/2 REVEAL Pediatric Study (NCT06152237) is testing TSHA-102 in girls, ages 5 to 8, who have Rett syndrome stage three (meaning symptoms are mostly stable).

The first part of the study will test two doses of the therapy in at least six patients (three per dose), with the goal of identifying the maximum dose that can be given without unacceptable side effects. If all goes well, the second part of the study will test the selected dose in a wider group including Rett patients as young as 3 years.

“By intervening early in disease, we believe TSHA-102 may provide significant therapeutic impact for pediatric patients,” said Berry-Kravis, the study’s principal investigator. “I look forward to evaluating this promising gene therapy and its impact on the lives of patients and their caregivers in the clinic.”

Dosing in the pediatric trial comes a few months after Taysha announced that the second patient had been dosed in the separate Phase 1/2 REVEAL Adult Study (NCT05606614) testing TSHA-102 in adolescents and adults with Rett syndrome. Dosing of the third participant was authorized late last year.

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Second adult with Rett given gene therapy TSHA-102 at lower dose

Multiple improvements seen in first 2 participants in adult study

Results from the first two participants showed the therapy was well tolerated up to 20 weeks into treatment in the first patient and six in the second. Also, efficacy data showed improvements in breathing, sleeping, motor function, socialization, and seizures.

“The pediatric trial will build on our ongoing REVEAL adolescent and adult trial, where early data demonstrated improvements across multiple clinical domains in adult patients with the most advanced stage of disease,” Nagendran said.

Recruitment is ongoing in both trials. The pediatric study is recruiting patients at the Rush center in Chicago, Illinois, with plans to open several other U.S. sites as well as sites in the U.K., after the company obtained regulatory authorization in that country. Meawhile the adult study is recruiting patients at a site in Montreal, Canada.