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

Phase 1/2 clinical trial now testing treatment candidate in Rett women

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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TSHA-102, an experimental gene therapy for Rett syndrome now being tested in clinical trials, has been granted fast track status by the U.S. Food and Drug Administration (FDA).

“We are pleased to receive FTD [fast track designation] from the FDA, which underscores the significant unmet medical need in patients with Rett syndrome and the potential of TSHA-102 to serve as a meaningful treatment option,” Sukumar Nagendran, MD, president and head of R&D at Taysha Gene Therapies, the company developing TSHA-102, said in a company press release.

Fast track designation is given to potential therapies for serious or life-threatening conditions. It is intended to accelerate a treatment’s development and regulatory review by providing benefits such as frequent meetings with the FDA.

“Currently, there are no approved disease-modifying therapies that treat the genetic root cause of the disease,” said Rumana Haque-Ahmed, Taysha’s senior vice president of regulatory affairs.

“Receiving FTD for important aspects of the disease is a critical milestone that furthers our ability to accelerate the development of TSHA-102 with the potential to address a serious condition and significant unmet medical need in patients living with this devastating disease,” Haque-Ahmed said, adding, “We look forward to having continued discussions with the FDA, with the goal of bringing TSHA-102 to patients as safely and expeditiously as possible.”

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

Taysha now planning trial of Rett gene therapy in children

Affecting girls almost exclusively, Rett syndrome is caused mostly by mutations in the MECP2 gene, which is located on the X chromosome — one of the sex chromosomes. The gene contains instructions for the production of the MeCP2 protein, which regulates other genes’ activities, and is involved in nerve cell function and communication.

The gene therapy, which is administered into the spinal canal fluid, uses a modified and harmless adeno-associated virus as a vehicle to deliver a shorter but functional version of the MECP2 gene. The delivered gene also includes a so-called switcher that ensures it is active only in nerve cells.

Because abnormally high MECP2 activity can be harmful, TSHA-102 uses a technology called miRARE that prevents overproduction of the MeCP2 protein in cells with a healthy version of the gene.

In a mouse model of Rett in prior studies, the gene therapy safely increased MeCP2 to normal levels in the brain, and extended the animals’ survival.

Now, a Phase 1/2 clinical trial (NCT05606614) called REVEAL is evaluating the safety, tolerability, and preliminary efficacy of two dose levels of TSHA-102 in women with Rett syndrome. The trial involves patients 18 and older, and is underway at a single site in Montreal, in Canada. Recruitment remains ongoing.

The first patient was dosed in June, and Taysha recently received the go-ahead to dose a second patient.

Early data from six weeks after dosing in the first individual treated in the trial showed no serious treatment-related side effects. Moreover, the preliminary data suggested improvements in the patient’s sleep, breathing, and motor skills.

“Initial data from the first adult patient in Canada with severe disease dosed with TSHA-102 is encouraging, and we expect to dose the second patient in our ongoing REVEAL Phase 1/2 adult trial in the current quarter,” Nagendran said.

We look forward to expanding the clinical evaluation to earlier stages of disease progression following recent FDA clearance to initiate clinical development of TSHA-102 in pediatric patients in the United States.


The company recently received FDA clearance to test the gene therapy in children with Rett syndrome, and the first patient is expected to be dosed early next year.

Also, Tasha earlier this month raised $150 million that will support the clinical testing of TSHA-102.

“We look forward to expanding the clinical evaluation to earlier stages of disease progression following recent FDA clearance to initiate clinical development of TSHA-102 in pediatric patients in the United States,” Nagendran said.

The gene therapy also has been granted orphan drug and rare pediatric disease designations by the FDA, and orphan drug status by the European Commission.