Skin-based gene therapy safe and effective in Phase 1 clinical trial for epidermolysis bullosa wounds

Written by Alexandra Thompson

An autologous gene therapy for healing wounds caused by the blistering skin disease epidermolysis bullosa, where genetically altered skin was grafted onto patients’ chronic wounds, appears to be safe and enhance healing following results of a Phase 1 clinical trial carried out by Stanford University Medical Center (CA, USA).

Clinicians from Stanford University Medical Center (CA, USA) have carried out a Phase 1 clinical trial in which genetically altered skin was grafted onto the chronic wounds of blistering skin disease epidermolysis bullosa patients. The team has announced that the treatment was well-tolerated and enhanced wound healing, marking the first time that a skin-based gene therapy has shown safety and efficacy in humans.

Epidermolysis bullosa is a genetic disease where type 7 collagen, which holds the upper and lower skin layers together, is not synthesized correctly. This results in the layers sliding across one another and causing blisters and large open wounds. Severe cases can be fatal in infancy, and although recessive dystrophic epidermolysis bullosa patients can live into adulthood, the condition is extremely painful and often results in squamous cell carcinoma, which develops as a result of the constant inflammation in response to the chronic wounds.

The study, carried out by associate professors of dermatology Peter Marinkovich and Jean Tang as well as senior scientist Zurab Si, was conducted on four adult patients with recessive dystrophic epidermolysis bullosa. “Our phase-1 trial shows the treatment appears safe, and we were
fortunate to see some good clinical outcomes,” said Tang. “In some
cases, wounds that had not healed for five years were successfully
healed with the gene therapy. This is a huge improvement in the quality
of life for these people.”

The team harvested and grew skin cells from each patient in vitro, and using viral delivery introduced a functional type 7 collagen gene into the cells in order to restore functional expression of the protein. The genetically corrected cells were then formed into sheets of skin that were surgically transplanted onto each patients’ chronic or new wounds in six locations.

They found that not only was the autologous graft tolerated, as determined by no immunological reaction occurring and the grafts staying in place, but blistering was inhibited, allowing wounds to heal. Furthermore, protein expression continued and wound healing was improved during a year of follow-up: after 3 months, 21 out of 24 grafts were intact, although this number dropped to 12 out of 24 after 1 year.

“Even a small improvement in wound healing is a huge benefit to the overall health of these patients,” said Tang. “For example, it may reduce the likelihood of developing squamous cell carcinoma that often kills these patients in young adulthood.”

The patients will continue to be monitored by the team throughout their lifetimes to assess any long-term effects of the grafts. Next steps for this research include enrolling pediatric patients into clinical trials to see if the approach can be used to intervene before chronic wounds develop.

Sources: Siprashvili Z, Nguyen NT, Gorell ES et al. Safety and wound outcomes following genetically corrected autologous epidermal grafts in patients with recessive dystrophic epidermolysis bullosa. JAMA 316(17), 1808—1817 (2016);;