Toward Stronger Skin: New Frontiers in Epidermolysis Bullosa (EB) Treatment

Written by: Jennifer Shon

Edited by: Spencer Diep, Serena Chen, Daniel Siahaan, and Amanda Benneh

Illustrated by: Julia Yelan Wang

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Introduction

Imagine that the simplest touch, brushing against one’s clothing, kneeling down for a prayer, or even a scratch from a dog, could trigger blistering and bleeding wounds. That is everyday life for people with Epidermolysis Bullosa (EB), a group of rare genetic disorders in which the skin and mucous membranes tear or blister at the slightest friction. EB, dubbed by some as “the worst disease you’ve never heard of,” [1] affects an estimated one in every 30,000 to 50,000 live births worldwide [2]. In severe cases, EB causes chronic wounds, scarring, infections, and a significantly increased risk of skin cancer—the physical, emotional, and financial burdens on patients and families are enormous.

Until quite recently, treatment for EB has been almost entirely palliative, merely consisting of daily wound care, infection prevention, pain control, protective bandaging, and monitoring. But over the past decade, scientific advances in gene therapy, cell therapy, and protein-replacement strategies have advanced, as we now see possibilities of long-term disease modification rather than just symptom management. This article examines how EB care is moving from basic support toward targeted molecular repair—and what that means for patients, clinicians, and the future of regenerative medicine.

Understanding Epidermolysis Bullosa

To understand EB, one must first understand the skin’s structure. The skin is composed of the outer layer (the epidermis) and beneath it the dermis; the two are held together by a thin “basement membrane zone” and specialized anchoring fibrils, which are slender fibers. In EB, mutations in one of at least 20 known genes weaken the structural proteins that glue the epidermis to the dermis [3]. These include key proteins like type VII collagen, laminin-332, and keratin 14 [3]. Without these anchors, even mild friction can cause the layers to separate and blister.

The main clinical diagnoses include EB Simplex (EBS), where blistering occurs within the upper epidermis (just below the skin surface), which tends to be milder [4] and Junctional EB (JEB), where the split occurs at the dermal-epidermal junction. Severely affected infants may die very early on from [4] Dystrophic EB (DEB), where the split is located deeper, below the basement membrane, often causing scarring and severe complications. Many cases are caused by mutations in the COL7A1 gene, which encodes type VII collagen [4], leads to Kindler syndrome, a mixed-type form with variable cleavage levels and photosensitivity [4].

EB is especially challenging because it affects the body’s most extensive organ—the skin—causing wounds to form all the time, from birth onward. Any effective therapy must address both the genetic root cause and the chronic wound environment (infection, inflammation, scarring). Moreover, treatments must be safe for lifelong use, since the skin constantly regenerates, and must treat all body regions (not just isolated patches). Treatment efficacy, immune safety, delivery logistics, and cost are all significant limitations.

Molecular Repair: Gene Therapy and Beyond

One approach is ex vivo gene-corrected skin grafts, where doctors take a patient’s own keratinocytes (skin cells) and correct the genetic defect using viral vectors, which act as delivery vehicles that insert a healthy version of the gene into the patient’s cells. These corrected cells are then expanded into sheets and grafted back onto the patient [5]. A case in 2017 detailed the efficacy of this treatment when a young boy—named the “Butterfly Boy”—underwent a skin grafting procedure for about 80% of his body with genetically modified cells [6]. In this procedure, researchers restored a functional LAMB3 gene using a retroviral vector, allowing the grafted skin to regenerate from corrected stem cells. Remarkably, the new epidermis was stable, blister-free, and capable of long-term self-renewal, with follow-up studies showing sustained clinical improvement years after treatment and no evidence of immune rejection or malignant transformation.

More recently, a topical gene therapy gel called beremagene geperpavec (B-VEC), more commonly referred to as Vyjuvek, uses a harmless herpes-simplex virus vector to deliver a functional COL7A1 gene directly to wounds of patients with Dystrophic EB [7]. In a Phase 3 trial, weekly B-VEC applications for 26 weeks achieved significantly better wound closure compared to placebo [8]. The FDA approved Vyjuvek in 2023, making it the first topical gene therapy for any skin disease [9].

Beyond gene delivery, researchers are testing antisense oligonucleotides—short DNA or RNA molecules that can “skip” faulty exons and restore partial protein function—and base-editing tools like CRISPR-Cas9 aim to permanently fix the mutation at its source. These techniques are still preclinical but show promise for durable, precise correction of EB mutations [4].

Restoring the Skin Through Cells and Proteins

Another potential, promising strategy is cell-based therapy, in which healthy or gene-corrected cells are transplanted to restore skin structure. Donor fibroblasts (connective-tissue cells) can be injected to locally increase collagen VII production and promote healing (10). Bone-marrow or hematopoietic stem-cell transplants (HSCT) aim for systemic correction, but carry high immune-rejection and graft-versus-host risks for patients [11]. Meanwhile, induced pluripotent stem cells (iPSCs)—adult cells reprogrammed to an embryonic-like state—can be gene-corrected and differentiated into keratinocytes or fibroblasts for autologous use. iPSCs have already shown success in other conditions, such as retinal disease and heart repair, making them a particularly versatile research tool [12].

For patients missing key structural proteins like collagen VII, scientists are testing recombinant protein replacement. The goal is to deliver lab-made collagen VII (rC7) topically or intravenously to reinforce the skin’s anchoring fibrils. Early clinical trials show improved skin integrity, though protein stability, dosing frequency, and efficient delivery remain major challenges [13].

Clinical Evidence and Limitations

Notably, in B-VEC’s Phase 3 trial, treated wounds closed at a much higher rate than untreated ones (71% versus 20% after three months) [8]. Gene-corrected skin grafts in earlier studies have remained stable for more than 5 years, showing sustained protein expression and no major safety issues [5]. In 2025, pz-cel (brand name Zevaskyn), an autologous cell-based gene therapy for DEB, received regulatory approval in the U.S., marking another enhancement within the field [14].

Despite this progress, there are serious limitations. Epidermolysis bullosa’s genetic diversity means no single therapy works for everyone [11]. The manufacturing process for gene-corrected grafts or viral gels is complex and expensive, causing accessibility to also be a concern. Additionally, ethical questions arise when using viral vectors in children or gene-editing tools that might have unanticipated effects, and lifelong monitoring and global equity in access are essential [10].

Integrating New Treatments into Patient Care

Translating these innovations into routine care takes detailed coordination for EB patients. For topical gene therapy like Vyjuvek, specialized EB centers handle wound preparation and weekly applications, whereas graft-based gene therapies require teams of dermatologists, surgeons, and geneticists to harvest, modify, and transplant cells. Supportive care—including infection control, nutrition, pain management, and psychological support—also is needed, and here, nonprofits like DEBRA International and the EB Research Partnership can help fund research, recruit patients, and advocate for treatment access [15].

However, we must note that even partial healing can change the lives of EB patients, as fewer blisters mean fewer dressings, less pain, and more freedom for them to stay active in daily life. The “butterfly boy” case, for example, visually showed us that regenerative therapies can restore independence and hope to families who once faced only lifelong suffering [6].

Conclusion

The future of EB research is bright with possibility, as scientists are working toward greater precision using base editors and CRISPR tools, with systemic delivery methods to reach internal tissues, and designing combinational treatments that pair gene, cell, and protein therapies for maximum effect. If successful, EB may become a model for curing other inherited skin and connective-tissue disorders. As one review notes, “Gene therapy appears to be the only treatment approach to potentially cure the disease” [4]. For those living with EB, the progress from blister management to molecular repair represents a “leap toward hope.” And as an EB patient myself—though in a milder form—I sincerely hope that these breakthroughs will ease the suffering of future patients, bring them a quality of life many of us could once only imagine.

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References

[1] Tran J, Cohen BA. Epidermolysis bullosa: the worst disease you’ve never heard of. Dermatology Times. Published October 28, 2025. https://www.dermatologytimes.com/view/epidermolysis-bullosa-the-worst-disease-you-ve-never-heard-of

[2] Prabhakaran H, et al. Dystrophic epidermolysis bullosa in a preschooler in a Middle Eastern country. Glob Pediatr Health. 2023. Published February 9, 2023. https://pmc.ncbi.nlm.nih.gov/articles/PMC9943966/

[3] Prodinger C, et al. Epidermolysis bullosa: advances in research and treatment. Exp Dermatol. 2019. Published October 2019. https://pmc.ncbi.nlm.nih.gov/articles/PMC6900197/

[4] Bruckner-Tuderman L. Structure and function of the dermal–epidermal junction and its role in epidermolysis bullosa. Exp Dermatol. 2023;32(2).

[5] Children’s Hospital of Philadelphia. Epidermolysis bullosa (EB). Published 2024. https://www.chop.edu

[6] Uitto J, et al. Translational advances in gene and protein therapies for epidermolysis bullosa. Int J Mol Sci. 2024;25(4):2243. doi:10.3390/ijms25042243

[7] Bauer JW, et al. Ex vivo gene therapy of epidermolysis bullosa: long-term clinical outcomes. Nat Med. 2023;29:789-798. doi:10.1038/s41591-023-02260-5

[8] CNN Health. Boy’s life saved by genetically engineered skin. Published 2017.

[9] Nyström A, et al. Topical beremagene geperpavec (B-VEC) for dystrophic epidermolysis bullosa. N Engl J Med. 2022;387:2211-2219. doi:10.1056/NEJMoa2201535

[10] PubMed Central. Clinical trial of B-VEC gene therapy. Published 2023. PMID: 40667654.

[11] US Food and Drug Administration. FDA approves first topical gene therapy for dystrophic epidermolysis bullosa. FDA press release. Published 2023.

[12] Koutsoukos SA, Bilousova G. Gene and cell therapy for epidermolysis bullosa and ichthyosis. Dermatol Ther. 2024.

[13] He R, et al. Cell therapy and stem cell transplantation for epidermolysis bullosa. Chin Med J. 2024;137(2).

[14] Takahashi K, Yamanaka S. Induced pluripotent stem cells in regenerative medicine. Cell Stem Cell. 2024;33(1).

[15] Woodley DT, et al. Recombinant human type VII collagen for epidermolysis bullosa therapy. J Invest Dermatol. 2022;142:299-310. doi:10.1016/j.jid.2021.07.014

[16] American Society of Gene and Cell Therapy. Pz-Cel gene therapy approved for dystrophic epidermolysis bullosa. ASGCT News. Published April 2025.

[17] DEBRA International. Clinical trials for epidermolysis bullosa. Published 2024. https://www.debra-international.org