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

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.

Management of Skin Lesions in Patients with Epidermolysis Bullosa by Topical Treatment: Systematic Review and Meta-Analysis

“…On the other hand, cell-based therapies involve the local or systemic application of cells that will produce the deficient binding proteins or differentiate into other cell lines to achieve this [ 61 , 65 ]. Cell therapy encompasses a variety of therapies including primary keratinocytes, fibroblasts, hematopoietic cells, and mesenchymal / stromal stem cells [ 11 ].…”

“…More than 30 subtypes are recognised, grouped into four main categories based predominantly on the cleavage plane within the skin, reflecting the underlying molecular anomaly: Simple EB, Junctional EB, Dystrophic EB, and Kindler EB. The simple type affects the most superficial layers, the junctional type (Type 2) is located in clefts in the lamina lucida of the skin, the dystrophic type (Type 3) manifests with blisters and can affect nails and skin, and finally, Kindler syndrome is characterised by keratoderma and, at times, is associated with mental retardation; in severe cases, EB can lead to early death [ 9 , 11 , 12 ] ( Appendix A.1 .).…”

Splicing Modulation via Antisense Oligonucleotides in Recessive Dystrophic Epidermolysis Bullosa

“…In RDEB, the target cells are the basal keratinocytes and dermal fibroblasts in the BMZ, which lies underneath several differentiated epidermal layers, including the stratum corneum. Similar to Vyjuvek ® , treating open RDEB wounds presents an opportunity to circumvent this problem [47]. However, ASOs still require proper packaging to protect them from degradation and facilitate their successful entry into cells [48].…”

Creation and characterization of novel rat model for recessive dystrophic epidermolysis bullosa: Frameshift mutation of the Col7a1 gene leads to severe blistered phenotype

“…In recent years, considerable efforts have been made to develop new forms of gene, cell, protein, and small molecule therapies, although current best clinical practice mostly just offers supportive care without cure [ 4 ]. Critical to all therapeutic developments is the need to develop suitable animal models that reflect the RDEB phenotype, its clinical course, and its disease complications.…”