A Stanford Medicine-led phase 3 clinical trial has demonstrated remarkable success for gene therapy skin grafts in treating epidermolysis bullosa (EB), with 81% of treated wounds showing at least half healing compared to just 16% of control wounds after 24 weeks. The breakthrough offers new hope for patients with this devastating genetic skin disorder that affects one in every 500,000 people.
Revolutionary Treatment for "Butterfly Children"
Severe dystrophic epidermolysis bullosa causes patients' skin to separate and blister from the slightest friction due to defects in the collagen VII gene. "Collagen VII is like a staple that attaches the top layer to the bottom layer of your skin," explained Jean Tang, MD, PhD, professor of dermatology at Stanford Medicine and the study's senior author. Without this molecular "staple," patients develop persistent wounds that can last for years, earning them the nickname "butterfly children" because their skin is as fragile as butterfly wings.
The phase 3 study included 11 patients with recessive dystrophic EB, all at least 6 years old, comparing 43 wound pairs where one wound received the gene therapy graft and the other received standard care. Results showed dramatic improvements: 65% of treated wounds were at least three-quarters healed compared to 7% of control wounds, and 16% of treated wounds completely healed while none of the control wounds achieved complete healing.
Personalized Gene Therapy Process
The treatment involves collecting a small biopsy of the patient's unwounded skin, which is then genetically engineered in the laboratory using a retrovirus to introduce a corrected version of the collagen VII gene (COL7AI). The modified cells are grown into credit card-sized skin sheets over 25 days before being surgically grafted onto wounds by plastic surgeons.
"Because each graft is created from the patient's own skin, the treatment provides healthy skin that matches the patients' own immune markers, preventing rejection of the grafts," the researchers noted. Patients typically stay hospitalized for about a week following the procedure.
Life-Changing Patient Outcomes
Study participant Brown, whose chronic wounds had prevented her from wearing dresses or attending social events, experienced transformative results. "It's honestly life-changing," Brown said. "I feel so much better." The treatment enabled her to attend her high school prom and pursue a career as a pharmacy technician - something she "never imagined" before.
Patients reported significant improvements in pain, itching, and blistering in grafted areas compared to control wounds. "Other patients have told me just how much of their life and attention had been focused on these painful wounds," Tang said. "To not have them is very freeing."
Two Decades of Stanford Research
The breakthrough represents the culmination of over 20 years of Stanford Medicine research that began in 2003 when Paul Khavari, MD, PhD, and Zurab Siprashvili, PhD, developed methods to safely genetically engineer EB skin cells. A phase 1 clinical trial led by Alfred Lane, MD, and Peter Marinkovich, MD, published in 2016, demonstrated early safety and effectiveness.
The treatment has been licensed from Stanford University by Abeona Therapeutics Inc., which will manufacture grafts for patients. The therapy will be available at five hospitals across the country, including Lucile Packard Children's Hospital Stanford.
Complementary Treatment Options
The skin grafts complement an existing gene therapy gel that has been available to EB patients since 2023. While the gel helps prevent and heal smaller wounds, the skin grafts address larger, more persistent wounds that require more intensive intervention.
"I hope that if these patients are diagnosed as infants and start the gene therapy gel, maybe they won't develop big wounds," Tang said. "But if the gels don't work and a wound does expand, the skin graft therapy is the right treatment."
Long-term Monitoring and Future Impact
Patients in the clinical trial will be followed for up to 15 years to monitor the continued success of the grafts. Researchers hope the treatment will reduce long-term risks for infections and skin cancer at graft sites, potentially modifying the entire disease trajectory for EB patients.
"It's important to let patients know: This may give you a fighting chance," Brown advised other patients. "If you are scared that you can't do things, it's going to help you get closer to living a normal life, or give you a better quality of life than you had previously."
