Sukumar Nagendran, MD, on Improving Rett Syndrome Symptoms in Adult Patients With Gene Therapy


The president and head of R&D at Taysha Gene Therapies discussed positive early results from the first 2 patients treated with gene therapy TSHA-102.

This is the second part of an interview with Sukumar Nagendran, MD. For the first part, click here.

“The first patient that we dosed was 20 years of age and had severe Rett syndrome in stage 4, and most of us are very surprised of because of the clinical response that we saw. Most of us, including the experts said, ‘You're not going to see a clinical response, get the safety data and go and move into the pediatric population.’ But what we noticed in the first patient was within 7 to 10 days there was a positive response on motor function and developmental milestones.”

In mid-2023, Taysha Gene Therapies dosed the first 2 patients in the first-in-human phase 1/2 REVEAL clinical trial (NCT05606614) evaluating TSHA-102, an investigational adeno-associated virus vector-based gene therapy intended to treat Rett syndrome.1,2 At that point in time, the trial was only open to adult patients, who have more advanced disease, and was primarily focused on the safety of the novel treatment. It was thought that the gene therapy was unlikely to have much efficacy in these older patients, and that promising efficacy results might not be seen until after safety was established and the gene therapy could be assessed in pediatric patients. To the surprise of the trial investigators, substantial improvements in the symptoms of both patients were observed.

In December 2023, about a month before Taysha announced the dosing of the first pediatric patient with TSHA-102 in the separate phase 1/2 REVEAL Pediatric Study (NCT06152237), CGTLive™ spoke with Sukumar Nagendran, MD, the president and head of research and development at Taysha, about the results seen in the first 2 adult patients to receive the gene therapy.3 Nagendran emphasized the surprising efficacy results seen in these patients. For example, he pointed out that the first patient showed improvements in areas such as ability to sit, hand strength, and verbal communication and that the second patient demonstrated improvements in balance and coordination while walking and in respiratory abnormalities.

1. Taysha Gene Therapies announces first patient dosed with TSHA-102 in the reveal phase 1/2 trial under investigation for the treatment of Rett syndrome. News release. Taysha Gene Therapies, Inc. June 5, 2023. Accessed January 12, 2024.
2. Taysha Gene Therapies reports third quarter 2023 financial results and provides corporate and clinical updates. News release. Taysha Gene Therapies, Inc.. November 14, 2023. Accessed January 12, 2024.
3. Taysha Gene Therapies announces first pediatric patient dosed with TSHA-102 in REVEAL phase 1/2 pediatric trial in Rett syndrome. News release. Taysha Gene Therapies, Inc. January 10, 2024. Accessed January 12, 2024.
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