Grant: Operating Grant:Bringing Rare Disease Gene Therapies to Clinical Trial Readiness

Skin injury such as open wounds must be treated rapidly to regenerate or replace the skin as early as possible in order to prevent infections. A rare skin disease called dystrophic epidermolysis bullosa is (DEB) is a genetic disorder that manifests as a lack of adhesion between the dermis and the epidermis and causes mucosa and epidermal detachments that can lead to severe complications. Around 300-500 persons are affected with EB in Canada. Genetically, DEB is caused by the lack of a protein called Collagen VII that normally is promoting adhesion (acting like a "glue") between the dermis and epidermis. DEB children are known as "Butterfly Children" as they have a skin that is as fragile as the wings of a butterfly. Sometimes DEB wounds are very painful and can persist for years or become aggressive skin cancer, which is a major cause of death. Until now, the treatment for these patients is palliative, mainly with bandages to protect epithelial wounds. That is why, DEB wounds and body parts are covered extensively with special non-sticky bandages that are very costly and hard to change. The present clinical trial I/II started in the Centre de recherche en organogenèse expérimentale de l'Université Laval/LOEX, CHU de Québec-UL hospital is consisting in the production of skin substitutes (reconstructed skin) from cells of DEB patients, cultured in the laboratory and genetically corrected by gene therapy to provide the missing collagen VII. The produced skin tissues will be grafted on the EB wounds to replace the lost skin. During the five last years, the effectiveness and the safety of this treatment was validated on human skin reconstructed in the lab and grafted on animals. It showed a graft take near 100%. Transplantation of reconstructed skin produced with the corrected cells is intended to provide permanent skin replacement to patients and improve their quality of life and lower the burden of this disease on the patient, his family, and the heath system overall.