Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a severe orphan genetic disease responsible for skin and mucosal detachments due to a loss of adhesion of the epidermis to the underlying dermis. The disease is caused by loss of function mutations of the COL7A1 encoding type VII collagen (C7) which forms anchoring fibers, which are essential structures for dermal-epidermal adherence. Current treatments are only symptomatic and do not effectively treat or prevent the occurrence of cutaneous and mucosal detachments responsible for local and systemic complications that threaten the vital prognosis.~EBGRAFT is a prospective open-label international monocentric phase I/II clinical trial. It aims to treat 3 adult subjects with RDEB, expressing residual C7 levels, by genetically corrected autologous skin equivalent grafts.~The skin equivalent consists of keratinocytes and fibroblasts from the patient, genetically corrected ex vivo with a secure Self INactivating (SIN) retroviral vector expressing the COL7A1 cDNA under the control of the ubiquitous human promoter EF1a.~Each patient will be grafted sequentially at Necker Hospital in Paris using autologous genetically corrected skin equivalents of approximately 300 cm2 (up to 6 grafts of 50 cm2 each).~The main objective is to evaluate the safety of autologous skin equivalent grafts genetically corrected with a SIN COL7A1 retroviral vector (RV) in adults with RDEB.~The secondary objectives are:~To evaluate the efficacy of transplanting autologous skin equivalent genetically corrected with RV SIN COL7A1 in adults with RDEB.~To evaluate the immune response against recombinant type VII collagen (C7).~This clinical trial should evaluate whether the grafting of these genetically corrected autologous skin equivalents is well tolerated and whether they restore normal dermal-epidermal adherence of the grafted areas. The proposed treatment aims to obtain a permanent correction of the grafted areas, allowing skin healing and reducing pain. It has the potential to reduce itching, to prevent the occurrence of blisters and skin detachments, reduce the risk of infections, the duration and cost of care and also the risk of development of squamous cell carcinomas in the grafted areas.
This phase I/II clinical trial aims to treat 3 adult subjects with Recessive Dystrophic Epidermolysis Bullosa, expressing residual C7 levels, by genetically corrected autologous skin equivalent grafts on selected areas (up to 300 cm2).