People with a blistering skin disease called dystrophic epidermolysis bullosa often suffer from large open wounds that last for years or decades. It’s an intensely painful condition, and medical treatment for it has been limited largely to palliative care.
Now, a double-blind, placebo-controlled clinical trial of a gene therapy gel developed at Stanford Medicine shows improved wound healing in 31 people with the disease, including 19 who were 18 years old or younger. Sixty-seven percent of wounds treated with the gel, which is applied to the skin during bandage changes, completely healed after six months of weekly applications, while only 22% of wounds treated with a placebo did so.
“After four months, I saw an improvement on a large wound on my back that I had for 20 years,” said trial participant Vincenzo Mascoli, 22. “After six months, the wound had healed completely and was much less painful.”
“This was a life-changing event for Vincenzo,” said Peter Marinkovich, MD, director of Stanford Medicine’s Blistering Disease Clinic. “Now he can bathe and sleep on his back without pain. This treatment made a huge difference in quality of life for Vincenzo and other trial participants.”
Marinkovich, an associate professor of dermatology, is the senior author of a study detailing the clinical trial results that was published Dec. 15 in The New England Journal of Medicine. Shireen Guide, MD, a pediatric dermatologist at Children’s Hospital of Orange County, California; Mercedes Gonzalez, MD, a pediatric dermatologist at Florida-based Pediatric Skin Research; and Isin Sinem Bağcı, MD, a basic life research scientist at the Stanford School of Medicine, are the lead authors of the study.
Marinkovich and his colleagues have applied to the Food and Drug Administration for approval of the gel, which is called B-VEC, as a treatment for dystrophic epidermolysis bullosa. It would be the first topical gene therapy treatment approved for use in the United States. The study was funded by Pittsburgh-based Krystal Biotech Inc., which is testing and developing the gel for clinical use.
The late-stage trial results mirror those seen in an earlier, smaller trial in nine patients conducted at the Stanford School of Medicine and published in Nature Medicine in March of 2022. That trial was the first to show that gene therapy vectors for skin diseases can be effective when applied topically and was the first trial of gene therapy in children with epidermolysis bullosa.
A missing protein
People with recessive dystrophic epidermolysis bullosa have a genetic mutation that renders them unable to make a protein called collagen VII, which binds the middle and outer layers of the skin together. Without this protein, the layers slide across each other, causing blisters that progress to severely painful open wounds. People with the condition are vulnerable to infections and skin cancer, and they often die in early adulthood.