Gene therapy for epidermolysis bullosa

Stanford Medicine scientists have developed two gene therapy treatments for a rare skin disease that causes severe blistering. Patients born with dystrophic epidermolysis bullosa, or EB, lack the gene for collagen VII, a protein that “staples” the skin together. Without it, their skin forms painful blisters at the slightest touch, many of which become long-term wounds.

Peter Marinkovich, MD, an associate professor of dermatology and director of Stanford Medicine’s Blistering Disease Clinic, has devoted his clinical and scientific career to helping EB patients lead better lives. In this Q&A, we asked Marinkovich to describe the gene therapies he helped develop.

When you started, what was missing from our toolbox for EB patients?

These patients live with pain all their lives. From day one, they have blisters on their bodies and pain that would incapacitate anyone, but they somehow find a way to live with it. They also have to live with exaggerated scarring. In particular, their hands can get scarred to the point where each hand is like a mitt encased in skin. This severely limits their daily activities.

For decades, all we could offer was supportive care — good wound care and good nutrition, because the turnover of their skin meant they needed nutritional support. But the blistering would still happen. We were helpless to stop it.

What key scientific advances made the new gene therapies possible?

When I was recruited to Stanford in the 1990s by Gene Bauer, an EB expert, researchers elsewhere were making great progress on identifying gene mutations responsible for EB. Gene said, “Instead of characterizing mutations, why don’t we devote our energy to developing therapies from these advances?”

We took a technology developed for burn victims: You can grow large amounts of skin from the patient’s own keratinocytes, a key type of skin cell. We also included a gene transfer step. Paul Khavari and his group, especially a researcher in his lab named Zurab Siprashvili, did one of the most difficult parts of this process: They made a viral vector that accommodates the very large collagen VII gene. We could get the corrected gene into the patient’s skin biopsy and multiply the cells to make a skin graft.

How did you show it works and is safe?

We started a clinical trial of the gene-corrected skin grafts around 2014, published results from the first four patients in JAMA in 2016, and got permission from the Food and Drug Administration to conduct a larger trial. I led this trial with Al Lane and, after Al retired, Jean Tang. We licensed the technology to Abeona Therapeutics Inc., which continued to prepare for a Phase 3 trial. That took a few years.

In the meantime, I started working on another technology, a topical gel gene therapy. It also uses a viral vector to deliver the corrected gene, but it’s less invasive. We just put this gel on the wound. There’s no manufacturing a graft, no going to the operating room or being hospitalized. Trials led by my team showed that the gel helped to durably heal EB wounds. In 2023, the gel, which is called beremagene geperpavec-svdt or B-VEC and is made by Krystal Biotech Inc., became the first FDA-approved gene therapy for epidermolysis bullosa.

The skin grafts, known as prademagene zamikeracel, received FDA approval in 2025. In the Phase 3 trial for the grafts, Jean Tang was the principal investigator evaluating wound healing and pain, while I was co-principal investigator ensuring that the grafting and other aspects of the trial were properly performed. We showed that the grafts helped heal patients’ wounds and significantly reduced their pain, itching and blistering. 

What long-term outcomes are you seeing?

We now have more than five years’ experience with each of the gene therapies for several of our clinical trial participants. Some have cleared up about 80% of the wounds on their bodies. It’s a huge, life-changing event.

We’re starting to see systemic effects. For the kids and teens, they grow more as their blisters clear, because their skin no longer demands so many nutrients. Chronic wound inflammation also caused anemia; as the wounds lessens, their hemoglobin increases, and they stop needing iron transfusions. And with healing, they are having much less pain. It’s so nice to see that.

What’s next?

The skin grafts are effective, but the process of getting them is complex, requiring surgery and a one-week stay in the hospital. For this reason, I recommend the gene therapy gel as a first step and, in severe patients who have more wounds than the gel can accommodate, I recommend using the gene therapy skin grafts as well as the gene therapy gel.

Now my team is working on an additional option for patients: a treatment that’s intermediate between these two therapies.

We’re excited that these treatments that were born and came to fruition at Stanford Medicine, from preclinical work all the way through FDA approval, have the potential to improve the lives of these vulnerable patients that we really care about.