2nd Rett patient to be dosed in trial of TSH-102 gene therapy

Taysha wins green light from committee to move ahead with testing

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Taysha Gene Therapies has received the go-ahead to continue clinical testing of TSHA-102, its gene therapy for Rett syndrome, and now is readying to dose a second patient, the company announced.

The experimental gene therapy is being evaluated in REVEAL (NCT05606614), a Phase 1/2 trial that’s recruiting up to 12 women with Rett, ages 18 and older, at a single site in Montreal, in Canada.

Following a review of data from the first patient dosed, an independent data monitoring committee, or IDMC — a group of experts who ensure the safety of a trial’s participants and the integrity of its data — recommended the study’s continuation.

“This recommendation was based on the analysis of initial clinical data from the first adult patient with Rett syndrome to receive TSHA-102,” Sukumar Nagendran, MD, Taysha’s president and head of research and development, said in a company press release.

“We are highly encouraged by the initial clinical observations, which support the transformative potential of TSHA-102 and mark important progress in our efforts to bring a gene therapy to patients and families living with Rett syndrome,”  Nagendran said.

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1st Rett patient had been given gene therapy in June

The first patient was dosed in June and monitored for review over the initial 42 days, or about six weeks, following treatment. The woman, since discharged from the hospital, has now completed multiple follow-up visits. A clinical update is expected later this month.

Sponsored by Taysha, the REVEAL trial is evaluating how safe, well tolerated, and effective the gene therapy is at either of its two doses. The trial is expected to last up to 63 months, or just longer than five years.

The green light from the monitoring committee was needed for the trial to move ahead after the pre-specified review.

“We thank the IDMC members for their guidance and are pleased with their recommendation to continue the REVEAL Phase 1/2 trial,” Nagendran said, adding, “A second patient is expected to be dosed in the third quarter of this year.”

Nearly all cases of Rett syndrome occur due to a mutation in MECP2, a gene located in the X chromosome. This gene codes for a protein called MeCP2, which is necessary for normal brain development.

Having even a few cells with mutations can be enough to cause the disorder’s symptoms. When someone has cells with a different genetic makeup within the body, it’s known as a mosaic pattern.

Gene therapy with TSHA-102 aims to deliver a healthy copy of MECP2 into cells. Because some cells may already produce MeCP2, and having too much of it can be harmful, it’s important to balance its levels carefully.

We thank the IDMC members for their guidance and are pleased with their recommendation to continue the REVEAL Phase 1/2 trial.

TSHA-102 combines miniMECP2, a shorter but working version of MECP2, with miRARE, a technology that allows controlled production of MeCP2, to avoid an excess of the protein.

In a preclinical study in mouse pups, TSHA-102 — which was carried aboard a virus called AAV9 — increased the levels of MeCP2 while causing no harm to cells that produced normal levels of the protein. It also had no negative effects on survival or general health.

The therapy is given as a single injection into the lower back. The two doses being tested will be given sequentially to different groups of patients. The highest tolerated dose will be used in further clinical testing.

“We look forward to providing an initial clinical update on the first patient at our second quarter corporate update conference call in mid-August,” Nagendran said.