Taysha links gene therapy to motor gains in small Rett study

Taysha Gene Therapies has unfurled more data in the developmental disorder Rett syndrome, linking its gene therapy to improvements in the first adults and children to receive low doses of the candidate. 

The Dallas-based biotech shared longer-term data on two adults and initial data on two children. Taysha had 52 weeks of follow up on one of the adults, plus 25 weeks of data on the other, as of the cutoff. The principal investigator tracked improvements in motor skills, communication and other measures over the follow-up periods.

The adult with 52 weeks of follow up, a 20 year old female with the severe phenotype, lost the ability to walk and sit unassisted aged eight years. After receiving TSHA-102, the patient regained the ability to sit unassisted and move their legs, Taysha said. Sukumar Nagendran, M.D., Taysha’s head of R&D, picked out other improvements in motor skills on a call with investors to discuss the data. 

“She could open her hands, dissociate her fingers, scratch her nose and touch a screen following treatment,” Nagendran said. “These sustained improvements in hand function, which are not typically observed in the natural history of Rett syndrome, are very encouraging and support the potential of TSHA-102 to bring meaningful therapeutic benefit to patients and caregivers.”

Social interest and vocalization improved, too, and the patient was able to sleep through the night for the first time in 20 years. Seizure events were stable on lower levels of anti-seizure medication relative to baseline. 

Taysha’s second adult patient, a 21-year-old female, had the milder phenotype and better motor skills at baseline than the first subject. In the 25 weeks after treatment, Taysha saw improved hand stereotypies, repetitive hand movements characteristic of Rett, for the first time since the patient regressed age three years. Posture, stability, social interest and breathing patterns also improved.

The biotech presented the results alongside initial data on two children, aged six and seven years, who received TSHA-102. The children were earlier in disease progression than the adults at the time of their treatment. Taysha has efficacy data from eight weeks after treatment in one patient and covering 12 weeks in the other subject. 

While the biotech has limited follow-up, it has seen signs of efficacy such as improved hand function and breathing patterns in both children. The child with 12 weeks of follow-up gained the ability to identify an object from memory and follow two unrelated commands. 

Patients with Rett have a broad spectrum of genetic backgrounds that result in a range of symptoms and varying levels of disease severity. Taysha CEO Sean Nolan said he sees reason to believe the gene therapy may be effective in a range of Rett patients. 

“The patients dosed with TSHA-102 across both trials have different genetic mutations and associated disease severity, ranging from mild to severe,” Nolan told investors. “We believe the improvements observed across consistent clinical domains, regardless of baseline disease severity, support the broad treatment potential of TSHA-102 across patients of different ages and genetic mutation backgrounds.”

Taysha is expanding the two trials in light of the data. The biotech has lowered the minimum age in the adolescent and adult study to 12 years and moved up to a higher dose. Taysha is positioned to escalate to the higher dose in the pediatric study once it has initial safety data from the trial in adolescents and adults, something it expects to happen in the third quarter.

The biotech is at the vanguard of efforts to develop a Rett gene therapy. Neurogene has a rival candidate in the clinic and is aiming to publish preliminary data this year. Alcyone Therapeutics' own prospect remains in preclinical development.