The Potential of Gene Therapy for Recessive Dystrophic Epidermolysis Bullosa

Conclusions and Clinical Perspectives of Gene Therapy for Recessive Dystrophic Epidermolysis Bullosa

Current clinical experience of gene therapy in RDEB has been limited to a small number of early-phase clinical trials. Considerable safety data and some evidence of early efficacy have been generated. It is evident that successful gene therapy depends on several factors, which include the nature of the underlying COL7A1 pathology, the target cell, and the practicality of facilities and resources. The advent of genome editing provides further hope and expectation of newer ex vivo and in vivo approaches to COL7A1 correction, although efficacy and off-target and unintended on-target effects still need to be reduced to a clinically acceptable level.

The complexity of underlying mechanisms in RDEB dictates a combinatorial approach for optimal outcome. Indeed, the potential to combine COL7A1 gene therapy with recombinant C7 protein replacement, cell therapy, and interventions that target the tissue inflammation and fibrosis that arise as a consequence of the RDEB disease pathobiology, are likely to be of most benefit for patients. Likewise, it is important also to focus on symptoms such as pain and itch in trying to improve quality of life for patients with RDEB. Nevertheless, gene therapy approaches for RDEB that target skin stem cells remains fundamentally important if a cure for this inherited blistering disease is to be achieved.

The British Journal of Dermatology. 2022;186(4):609-619. © 2022 Blackwell Publishing