Epidermolysis bullosa (EB) is a group of rare genetic disorders for which significant progress has been achieved in the development of molecular therapies in the last few decades. Such therapies require knowledge of mutant genes and specific mutations, some of them being allele specific. A relatively large number of clinical trials are ongoing and ascertaining the clinical efficacy of gene, protein or cell therapies or of repurposed drugs, mainly in recessive dystrophic EB. It is expected that some new drugs may emerge in the near future and that combinations of different approaches may result in improved treatment outcomes for individuals with EB.
Key PointsRemarkable progress has been made in understanding the molecular genetics and underlying pathomechanisms of epidermolysis bullosa (EB) forming the platform for development of treatments.Gene-replacement approaches, particularly delivery of COL7A1 to the skin of patients with severe dystrophic EB, type VII collagen replacement, skipping of exons and read-through of premature termination codons are currently in clinical trials.Preclinical research explores the applicability of new strategies in regenerative medicine (e.g., induced pluripotent stem cells) and genome editing (e.g., CRISPR/ Cas9).Particular effort is focused on severe dystrophic EB, characterized by extensive scarring and aggressive squamous cell carcinomas. Small molecules repurposed to reduce fibrosis, and the multikinase inhibitor rigosertib-for the treatment of recessive dystrophic EB squamous cell carcinomas-are being tested in clinical trials.