1 Introduction
Inherited epidermolysis bullosa (EB) comprises a group of rare genetic disorders that affect *500,000 people across the world. The different forms of EB are characterized by variable degrees of trauma-induced fragility of the skin and mucosae, blister formation, and abnormal wound healing. EB is caused by mutations in at least 18 distinct genes that encode various structural and signaling proteins at the dermal-epidermal junction and within the epidermis.[1] Clinically, there are four main types of EB: simplex, junctional, dystrophic, and Kindler syndrome, although the classification of EB continues to evolve with inclusion of new clinicopathologic entities and recognition of up to 30 clinical subtypes.[2]
Currently, there is no effective therapy or cure for EB. Best practice treatments include multi-disciplinary healthcare and social welfare support.[3,4] But the burden of disease is enormous: some forms of EB require daily changes of wound dressings that can take several hours to perform and strenuous efforts are needed to maintain adequate mobility and nutrition, and to limit complications such as skin infection, scarring, dental caries, dysphagia, constipation, and skin cancer. There is a desperate need to develop novel therapies that modify disease biology and offer hope for a better life for patients.
Thankfully, over the last decade, a number of important advances have been made that are bringing new treatments closer to the clinic. Here, we take recessive dystrophic EB (RDEB) as an example to highlight some recent therapeutic progress. RDEB is caused by homozygous or compound heterozygous mutations in the type VII collagen gene (COL7A1).[5] Type VII collagen (C7) is secreted by both dermal fibroblasts and epidermal keratinocytes into the extracellular space, where it assembles into anchoring fibrils that secure adhesion between epidermis and dermis.[6,7] Individuals with RDEB usually present with generalized blistering from birth or shortly thereafter (Fig. 1). This form of EB is one of the clinically most severe inherited diseases and is frequently accompanied by lifethreatening infections, joint contractures, esophageal strictures, and aggressive squamous cell carcinomas.[2] A key therapeutic goal is to try to restore C7 function in the skin, or to compensate for its loss by reducing the downstream complications of RDEB. To that end, some new potential treatments are entering the clinical arena, including gene, protein, and, in particular, cell therapies.
Am J Clin Dermatol. 2014;15(1):1-6. © 2014 Adis Springer International Publishing AG
