Integrated Management Strategies for Epidermolysis Bullosa: Current Insights

Abstract

Epidermolysis bullosa (EB) is a group of rare genodermatoses that is characterized by skin fragility resulting from minor trauma. There are four major subtypes, namely, EB simplex, junctional EB, dystrophic EB and Kindler EB, depending upon the localization of defective protein and resulting plane of blister formation. The phenotype is heterogeneous in terms of severity and majority of them present at birth or neonatal period. Currently, the treatment is mainly supportive and requires multidisciplinary care. The complex molecular pathology creates difficulty in discovering a unified curative treatment approach. But with arduous efforts, significant progress has been made in the development of treatment strategies in the last decade. The management strategies range from targeting the underlying causative factor to symptom-relieving approaches, and include gene, mRNA, protein, cell and combination therapies. In this review, we enumerate the promising approaches that are currently under various stages of investigation to provide effective treatment for patients with EB.

Keywords: antisense oligonucleotides; blistering skin disorder; epidermolysis bullosa; gene editing; gene replacement; readthrough therapies; revertant mosaicism; siRNA therapeutics; spliceosome-mediated RNA trans-splicing; squamous cell carcinoma.

Figure 1

Various novel therapeutic strategies that are being explored in management of epidermolysis bullosa.

Figure 2

The 4 layers of skin with dermo-epidermal junctions and corresponding genes involved in the maintenance of their integrity. Basal keratinocytes secrete KRT5 and KRT14, which form the intermediate filaments and interact with other cytoskeletal proteins in epidermis and lamina lucida to provide integrity and adhesion. Gain of function mutations in KLHL24 gene leads to breakdown of intermediate filaments. AON: Anti sense oligonucleotide, SMaRT: Spliceosome-mediated RNA trans-splicing.