New Options to Manage Epidermolysis Bullosa

Abstract

RDEB is a genetic skin disorder involving COL7A1, the gene encoding C7, which is a component of the fibers anchoring the epidermis to the dermis. Affected patients (about 1.35 per million persons in the United States) experience lifelong painful itching, blistering, fibrosis, impaired healing, and scarring, with increased likelihood of infection and cancer. RCT involving those affected by RDEB are rare with limited sample sizes due to the low prevalence of this genetic disorder. Treatment with topical or systemic agents has not consistently improved patient outcomes. Therapies focused on replacing C7 using autologous bone marrow or keratinocyte grafts have been difficult, with high complication rates, and have been met with mixed success. Recent HSV-1 vector research led to development of HSV-1 vectors capable of transferring the COL7A1 coding sequence to keratinocytes and fibroblasts in vitro and to mice deficient in C7, as well as to RDEB human skin xenografts. This research offered new opportunities for gene therapy for patients with RDEB. In this final Evidence Corner, readers are invited to consider the implications of 2 small RCTs that suggest fruitful avenues for RDEB research and practice. The first study describes a pioneering phase 1 and 2 RCT of topical gene therapy for RDEB. The second study describes a small crossover RCT exploring the effect of topical calcipotriol (VD3) ointment on wound healing and pruritis in patients with RDEB.