TSHA-102 gene therapy leads to improvements for 1st adult patient

Clinical testing in children also cleared by US regulators

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The first woman with Rett syndrome given the gene therapy TSHA-102 has experienced improvements in her sleep, breathing, and motor skills in the first weeks since the treatment.

That’s according to new data announced by Taysha Gene Therapies, the company developing TSHA-102.

“We believe the initial safety profile and significant clinical improvements seen in the first adult patient with severe disease four weeks post-treatment reinforces the transformative potential of our gene therapy to address the root cause of Rett syndrome,” Sean P. Nolan, board chairman and CEO of Taysha, said in a company press release.

“We are highly encouraged by the initial data for TSHA-102 and are focused on continuing to explore its therapeutic potential,” Nolan said.

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Taysha secures US regulatory permission to test gene therapy in children

In addition to announcing these positive data from the first adult patient treated, Taysha stated that it has secured regulatory permission in the U.S. to start clinical development of the therapy in children. The company is also working to secure similar permission in the U.K. These steps “will expand our clinical evaluation to children with earlier stages of disease progression,” Nolan said.

Rett syndrome is caused by mutations in the gene MECP2, which is located on the sex-determining X chromosome. The condition occurs primarily in girls, with even a few cells with mutations being sufficient to cause disease symptoms.

TSHA-102 is designed to deliver a healthy copy of the MECP2 gene to the body’s cells. Since abnormally high MECP2 activity can cause problems, the gene therapy includes a technology called miRARE, which helps to regulate the MECP2 gene and prevent it from being overactive in cells that already have an active functional copy of the gene. The therapy is administered into the spinal canal fluid.

Taysha is sponsoring a Phase 1/2 study called REVEAL (NCT05606614) to test two doses of TSHA-102 in women with Rett syndrome, ages 18 and older. Recruitment is ongoing at a center in Montreal, Canada.

The first participant in REVEAL was dosed in June, and Taysha recently received clearance to dose a second patient, which is expected to happen in the next month or so.

The patient was able to sit unassisted for the first time in over a decade, and she demonstrated the ability to unclasp her hands and hold an object steadily for the first time since infancy.

No serious treatment-related side effects reported in patient after 6 weeks

No serious treatment-related side effects have been reported in the first patient six weeks after receiving TSHA-102.

“Importantly, these early data indicate that the miRNA-Responsive Auto-Regulatory Element (miRARE) technology is mediating MECP2 expression in the [brain and spinal cord] on a cell-by-cell basis, supporting the regulatory control of miRARE,” Nolan said.

Six-week data also suggested improvements in the patient’s motor skills. For the first time in years, the woman is able to sit up unassisted for three minutes. Her hand function has also improved, allowing her to hold objects, unclasp her hands, and use her fingers to touch a screen.

In addition to motor function improvements, the patient has shown more vocalizations and interest in socialization, and her breathing patterns and sleep quality have improved.

“Prior to treatment, the patient was in a constant state of hypertonia [excess muscle tone], had limited body movement, required constant back support, and had lost fine and gross motor function early in childhood,” said Elsa Rossignol, MD, principal investigator of the REVEAL study at the Université de Montréal.

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Patient rated as being ‘much improved’

“The patient was able to sit unassisted for the first time in over a decade, and she demonstrated the ability to unclasp her hands and hold an object steadily for the first time since infancy,” Rossignol said. “I believe that the patient achieving these milestones so early in treatment, coupled with the improvements in breathing patterns and quality of sleep that we have observed, are highly encouraging and support the potential of TSHA-102.”

In clinician-rated measures, the patient was rated as being “much improved” compared to her status prior to gene therapy. The clinician-rated severity of her condition also improved from “severely ill” to “markedly ill.”

Her scores on the Rett Syndrome Behavior Questionnaire, a measure of symptom severity, decreased from an initial score of 52 to 29, suggesting improvement. No notable changes were reported in a clinician-rated measure of Rett behaviors called the Revised Motor Behavior Assessment.

“The efficacy response observed following treatment with TSHA-102 in the first adult with an advanced stage of Rett syndrome is promising,” Rossignol said.