Dr. Anna Bruckner discusses important things to remember and consider when treating epidermolysis bullosa, as well as pipeline gene therapies that could help change the course of the disease.
Anna L. Bruckner, MD, MSCS, Professor of Dermatology and Pediatrics, University of Colorado School of Medicine and Co-director of the regional center of excellence for epidermolysis bullosa at Children’s Hospital Colorado in Aurora, Colorado.
“It’s important to understand that epidermolysis bullosa (EB) is not a homogenous condition. The term EB refers to a group of genetic disorders that have the common feature of blistering or skin fragility. But there are a range of severities that can be seen with that,” said Anna Bruckner, MD, MSCS, who presented “Epidermolysis Bullosa: How to Treat” at the Masters of Pediatric Dermatology Symposium in Miami Beach, Florida.
EB classifications include EB simplex, where blistering occurs in the epidermis; junctional EB, where the blistering occurs in the proteins that sandwich the epidermis and dermis together; and dystrophic EB, where the blistering involves the superficial dermis, said Dr. Bruckner.
“Depending on the particular gene or protein affected, the symptoms and severity can vary. Making an accurate diagnosis through genetic testing, first and foremost, is really important. That is going to help guide the prognosis and particular treatment for the individual patient.”
Skin and Wound Care
The common feature of all EB disorders is blistering or erosions of the skin and mucous membrane, said Dr. Bruckner.
“Much of the care of EB includes skin and wound care. We teach new families how to pop blisters to keep them from spreading. There are currently a range of different bandages that are used to help promote wound healing and protect the skin.”
These are typically made of silicone, which provides tackiness to adhere to skin but also is nontraumatic when released from the skin, according to Dr. Bruckner.
“This has really been a game-changing approach to wound care for our patients, who have to do these dressing changes every day or every other day.”
Beyond the Skin
Beyond wound care, it’s important to keep EB’s other manifestations in mind, she said.
“These can occur particularly with the more severe forms of EB—junctional EB and recessive dystrophic EB. There are lots of different impacts on patients in terms of their overall health. They have difficulty eating and difficulty swallowing. They have, in some cases, difficulty absorbing sufficient calories. So, paying close attention to their nutrition is really important.”
Supporting nutritional needs might mean that some patients need to have a gastrostomy tube placed or dilations to widen a narrowed esophagus, said Dr. Bruckner.
“Severe forms of EB are really multisystem disorders, not just skin disorders. And it really does take a village to care for those patients.”
In the Pipeline
It’s an exciting time in EB research, said Dr. Bruckner.
“There have been a lot of new approaches to treatment that will hopefully help to modify the course of the disease or, dare we say, lead to a cure down the road. Much of the promise has been in the area of gene therapy.”
In the recessive forms of EB, the genetic abnormality leads to a lack of a protein in the skin, she said.
“If we can replace that faulty gene, the individual’s body would then be able to make the appropriate protein which would then help to hold the skin together.”
Progress has been slow, but some approaches to gene therapy are starting to show promise, said Dr. Bruckner.
“In my talk, I reviewed examples of the first approaches for gene therapy, which involve taking cells from an affected patient and, in lab, reintroducing a complete copy of the gene that was affected; then allowing the corrected cells to grow into sheets, which can be transplanted back onto patients.”
The approach has been used successfully on a few patients in Europe with junctional EB. And there is currently a phase 3 clinical trial in the U.S. of that same approach to treat wounds in patients with recessive dystrophic EB (Abeona Therapeutics), she said.
According to Dr. Brckner, the same approach can be used with fibroblasts that are formed in the dermis or the connective tissue layer of the skin. There is a clinical trial currently in the U.S. looking at correcting fibroblasts (Castle Creek Biosciences), then injecting them back into wounds in patients with EB, in hopes of leading to more durable wound healing.
“Krystal Biotech is using a different approach to gene therapy where they are using the herpes simplex virus (HSV) as a vector to reintroduce type 7 collagen back into the skin. Their approach takes the HSV virus, which has been slightly modified so it is not infectious but also includes a full-length copy of the collagen 7 gene. By applying the product as a liquid to wounds, the virus can then be temporarily taken up by the skin cells, so they make collagen 7.”
Results of the phase 3 data were recently published in the New England Journal of Medicine, she said.1
“There was a clear difference in terms of durable wound healing in the wounds treated with the medication versus wounds treated with a placebo. As a community we are keeping our fingers crossed that this treatment will be approved this year.”
There’s more work to be done, but these are good first steps, said Dr. Bruckner.
“We still need to be thinking beyond [wounds] in terms of, how can we address some of the other manifestations of EB?”
As of early 2023, the state of EB care in the U.S. remains for the most part palliative, said Dr. Bruckner.
“There are no approved disease modifying treatments for EB, yet. The current care includes wound care, nutritional support, monitoring for complications, and trying to manage pain and itching, which are debilitating symptoms for patients. That’s not to say that we can’t improve health with this approach to care, but at the same time I think patients are hungry for something else.”
Reference:
Guide SV, Gonzalez ME, Bağcı IS, et al. Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa. N Engl J Med. 2022;387(24):2211-2219. doi:10.1056/NEJMoa2206663.
Disclosures: Dr. Bruckner has been an investigator for Castle Creek Biosciences.