Topical Gene Therapy Promotes Healing of Inherited Skin Disease

The rare skin disease recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in the COL7A1 (collagen type VII a1 chain) gene. This gene normally encodes an important component of the basement membrane that connects the epidermis and dermis. RDEB is thus characterized by skin blistering, fibrosis, and susceptibility to infection and cancer. Irene Gurevich, PhD, Stanford University School of Medicine, and colleagues there and elsewhere, including Kryatal Biotech, developed a topical gene therapy, beremagene geperpavec (B-VEC), for RDEB in which COL7A1 coding sequences are delivered by inactivated herpes simplex virus type 1 (HSV-1) to the skin. Having established that B-VEC restored COL7A1 protein expression in preclinical models, the authors carried out a phase 1/2 trial in nine RDEB patients. B-VEC or placebo was repeatedly applied to matched wounds, and B-VEC promoted COL7A1 expression and wound closure. There was also evidence of correct epidermis-dermis organization. This work was described in an open-access article published on March 28, 2022 in Nature Medicine. The article is titled “In Vivo Topical Gene Therapy for Recessive Dystrophic Epidermolysis Bullosa: A Phase 1 And 2 Trial. This posting is based on a Nature Medicine summary authored by Gemma Adlderton, PhD.