Spinal Delivery Of Taysha's Gene Therapy Shows Promise In Rare Childhood Neurodegenerative Disease

An investigational gene therapy, dubbed scAAV9/JeT-GAN, for a rare neurodegenerative disease, giant axonal neuropathy (GAN), that begins in early childhood was well tolerated and showed signs of therapeutic benefit in a Phase 1 trial led by the National Institutes of Health (NIH). 

The study was supported by NINDS and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Hannah’s Hope Fund, Taysha Gene Therapies Inc TSHA, Bamboo Therapeutics/Pfizer Inc PFE, Child Neurology Society, and the American Society of Gene and Cell Therapy. 

Fourteen children with GAN, ages 6 to 14 years, were treated with gene transfer therapy and then followed for about six years to assess safety. 

The gene therapy, which utilizes a modified virus to deliver functional copies of the defective GAN gene directly into the spinal fluid, showed tolerance and potential therapeutic benefits in 14 children aged 6 to 14. The trial demonstrated encouraging signs of safety and efficacy.

Participants in this “first-in-human” trial, which began in 2015, received a single dose of the gene therapy through an injection into the fluid surrounding the spine. 

The first two patients received the lowest dose of the gene transfer, which was increased in subsequent patients. 

Four dose levels were tested over the trial, which were estimated based on results from studies in animal models. 

It is the first time a gene therapy has been administered directly into the spinal fluid, allowing it to target the motor and sensory neurons affected in GAN. 

At some dose levels, the treatment appeared to slow the rate of motor function decline. The findings also suggest that regeneration of sensory nerves may be possible in some patients.

Only one serious adverse event – a fever – was potentially linked to the gene therapy. 

The treatment resulted in 129 related adverse events of lesser seriousness, including headache, back pain, irregular heart rhythms, and inflammation in spinal fluid treated with corticosteroids. 

Two patients who were older and received the lowest-dose therapy died during the study period due to events related to their underlying disease.  

In addition to safety, the researchers found that with increasing dose levels, the probability of any slowing of motor decline was 44%, 92%, 99%, and 90%, respectively. 

As GAN progresses, electrical measures of sensory nerves decline and eventually disappear. With gene therapy, 6 of 14 patients regained sensory nerve response after treatment—electrical measures increased, stopped declining, or became measurable after being absent.

Price Action: TSHA shares are up 5.24% at $3.12 on the last check Thursday.