'Butterfly disease' makes the skin incredibly fragile, but a new gene therapy helps it heal

"Butterfly disease" is a rare genetic condition that causes people's skin to bubble up in blisters under the slightest pressure. Now, in a late-stage clinical trial, researchers have shown that a gel containing DNA can help mend these patients' wounds and prevent further damage. 

These results, published Wednesday (Dec. 14) in the New England Journal of Medicine, and those of a previous smaller trial, are now being reviewed by the U.S. Food and Drug Administration (FDA). The agency should come to a decision about approving the therapy by mid-February 2023, according to Krystal Biotech, the trial's sponsor.

There are currently no approved treatments for those with butterfly disease, scientifically known as "epidermolysis bullosa" (EB). Doctors, patients and their caregivers can only tend the blisters as they arise, trial leader Dr. M. Peter Marinkovich, director of the Blistering Disease Clinic at Stanford Health Care and an associate professor of dermatology at the Stanford University School of Medicine, told Live Science. This involves cleaning the skin wounds, covering them in ointments and dressings, and changing out those dressings daily — an often painful process for the patient. "And that's all the tools, right now, we have to treat these patients," Marinkovich said. 

Patients' wounds often reopen during healing and can remain open for months or even years. Chronic wounds and a build-up of scar tissue puts patients at risk of life-threatening infections, limb deformities and a skin cancer called squamous cell carcinoma.

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The approval of the new gene therapy, called beremagene geperpavec (B-VEC), would mean that "we're finally able to bring something to this patient population to actually help them," Marinkovich said.

B-VEC is designed to treat a subtype of butterfly disease known as "dystrophic EB," caused by mutations in a gene called COL7A1. The gene normally codes for a type of collagen — specifically a rope-like protein that helps anchor the outermost layer of skin to the one beneath. People with dystrophic EB lack this stabilization, so their skin layers rub against each other and blister.

Dystrophic EB comes in two forms: dominant, in which people inherit one mutant copy of COL7A1; and recessive, in which they inherit two, one from each parent. All but one patient in the new trial had recessive dystrophic EB, one of the most severe forms of EB.

B-VEC works by delivering working copies of COL7A1 directly into patients' wounded skin. It contains a version of the cold sore virus, herpes simplex virus 1, that is modified so it can’t replicate in human cells and carries two copies of COL7A1. The herpes virus is a good fit for gene therapy because it's big enough to carry large snippets of DNA and has the ability to evade the immune system, meaning therapies containing the virus are less likely to trigger harmful reactions after repeated use, Marinkovich said. 

In the trial, 28 patients had B-VEC applied to one of their wounds once a week for about six months, while another wound of similar size was treated with a placebo gel. After three months, 71% of the B-VEC-treated wounds had completely healed, compared with 20% of the placebo-treated ones, and the healing rates were similar at six months.

"This is a devastating disease with minimal current treatment options, and the gene therapy clearly accelerated the healing of patient wounds," said David Schaffer, director of the Berkeley Stem Cell Center and of QB3-Berkeley at University of California, Berkeley, who was not involved in the trial. "This study is consistent with prior reports on this therapy, though the longer timeframe of the study show[s] that the effect on individual wounds is durable for at least 6 months. This was a very successful study," Schaffer told Live Science in an email. 

The gel was applied in a clinic during the trial, but if the treatment is approved it could easily be used at home during routine wound-dressing changes, Marinkovich said. This should make the therapy more accessible than other experimental EB therapies, which involve skin grafts and engineered stem cells. Although B-VEC would be an ongoing treatment rather than a permanent cure for the disease, "I can see this being utilized to help a lot of EB patients," he said. 

In the future, the team plans to develop different versions of the therapy that can be easily applied to harder-to-reach tissues where patients sometimes develop blisters, such as the lining of the esophagus and membranes around the eyes, Marinkovich added.