Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jun 14:19:455-473.
doi: 10.2147/TCRM.S386923. eCollection 2023.

Innovations in the Treatment of Dystrophic Epidermolysis Bullosa (DEB): Current Landscape and Prospects

Ping-Chen Hou #  1 , Nathalie Del Agua #  2   3 , Su M Lwin  4 , Chao-Kai Hsu  1   2   3 , John A McGrath  1   3   4
Affiliations
Review

Innovations in the Treatment of Dystrophic Epidermolysis Bullosa (DEB): Current Landscape and Prospects

Ping-Chen Hou et al. Ther Clin Risk Manag. .

Abstract

Dystrophic epidermolysis bullosa (DEB) is one of the major types of EB, a rare hereditary group of trauma-induced blistering skin disorders. DEB is caused by inherited pathogenic variants in the COL7A1 gene, which encodes type VII collagen, the major component of anchoring fibrils which maintain adhesion between the outer epidermis and underlying dermis. DEB can be subclassified into dominant (DDEB) and recessive (RDEB) forms. Generally, DDEB has a milder phenotype, while RDEB patients often have more extensive blistering, chronic inflammation, skin fibrosis, and a propensity for squamous cell carcinoma development, collectively impacting on daily activities and life expectancy. At present, best practice treatments are mostly supportive, and thus there is a considerable burden of disease with unmet therapeutic need. Over the last 20 years, considerable translational research efforts have focused on either trying to cure DEB by direct correction of the COL7A1 gene pathology, or by modifying secondary inflammation to lessen phenotypic severity and improve patient symptoms such as poor wound healing, itch, and pain. In this review, we provide an overview and update on various therapeutic innovations for DEB, including gene therapy, cell-based therapy, protein therapy, and disease-modifying and symptomatic control agents. We outline the progress and challenges for each treatment modality and identify likely prospects for future clinical impact.

Keywords: blister; cell therapy; fibrosis; gene therapy; inflammation; skin.

PubMed Disclaimer

Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Clinical manifestations of DEB patients. (A) Generalized blistering and ulceration, (B) microstomia, (C) pseudosyndactyly, and (D) cutaneous squamous cell carcinoma, in RDEB. (E and F) Scattered, semi-confluent, erythematous or hyperpigmented prurigo-like papules and plaques of varying severity, as well as toenail dystrophy, in DDEB.
Figure 2
Figure 2
Schematic illustration of multimodal treatment options for DEB patients. Various treatment modalities for DEB include gene therapy, cell-based therapy, protein therapy, disease-modifying and symptomatic control agents. (Blue/Pink: has been tried in RDEB/DDEB; Light blue/Light pink: has not been tried in RDEB/DDEB but has potential for treatment; Grey: not suitable).
Figure 3
Figure 3
Schematic illustration of the clinical status (entering preclinical or clinical stage) of various DEB treatments.
Figure 4
Figure 4
Treatment effect of intravenous allogeneic bone-marrow derived mesenchymal stem cells infusion in RDEB. The upper back of a 26-year-old patient with severe RDEB demonstrates improved wound healing and less inflammation 100 days after intravenous allogeneic mesenchymal stem cells infusion.
Figure 5
Figure 5
Treatment effect of intravenous biweekly dupilumab injections in DDEB. A 59-year-old patient with DDEB (EB pruriginosa) displays flattening and less erythema of the prurigo-like papules and nodules on both lower legs after biweekly dupilumab injections for 3 months. The itch numerical rating score also decreased from 8.5 to 3.5.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bardhan A, Bruckner-Tuderman L, Chapple IL, et al. Epidermolysis bullosa. Nat Rev Dis Primers. 2020;6(1):78. doi:10.1038/s41572-020-0210-0 - DOI - PubMed
    1. Has C, Bauer JW, Bodemer C, et al. Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br J Dermatol. 2020;183(4):614–627. doi:10.1111/bjd.18921 - DOI - PubMed
    1. Petrof G, Papanikolaou M, Martinez AE, et al. The epidemiology of epidermolysis bullosa in England and Wales: data from the national epidermolysis bullosa database. Br J Dermatol. 2022;186(5):843–848. doi:10.1111/bjd.20958 - DOI - PubMed
    1. Nyström A, Bornert O, Kühl T, et al. Impaired lymphoid extracellular matrix impedes antibacterial immunity in epidermolysis bullosa. Proc Natl Acad Sci U S A. 2018;115(4):E705–E714. doi:10.1073/pnas.1709111115 - DOI - PMC - PubMed
    1. Tartaglia G, Cao Q, Padron ZM, South AP. Impaired wound healing, fibrosis, and cancer: the paradigm of recessive dystrophic epidermolysis bullosa. Int J Mol Sci. 2021;22(10):5104. doi:10.3390/ijms22105104 - DOI - PMC - PubMed