title: Type VII Collagen Replacement Therapy in Recessive Dystrophic Epidermolysis Bullosa-How Much, How Often?
abstract: Recessive dystrophic epidermolysis bullosa is a devastating blistering disease caused by mutations in the COL7A1 gene, which encodes type VII collagen, the major component of anchoring fibrils. The anchoring fibrils in patients with recessive dystrophic epidermolysis bullosa can be morphologically altered, reduced in number, or absent entirely. There is no specific treatment for this disease, but recent advances in gene, protein replacement, or cell-based therapies, with the purpose of delivering functional type VII collagen to the skin, have shown encouraging results in both preclinical and clinical settings. One critical issue is the stability of type VII collagen in anchoring fibrils, which will ultimately determine the dose and frequency of administration of the missing protein. Kühl et al. attempted to determine the half-life of type VII collagen in the skin, tongue, and esophagus of genetically altered mice that express type VII collagen constitutively, but with its expression abrogated by genetic manipulation. Their results revealed a half-life much shorter than previously anticipated, some 30 days. These findings have implications for strategies to be used for protein replacement therapy, and they also suggest that the basement membrane components at the dermal-epidermal junction are subject to ongoing remodeling and turnover.
authors.affiliation: Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: South
authors.affiliation: Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Electronic address: jouni.uitto@jefferson.edu.
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D024143:Collagen Type VII / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016108:Epidermolysis Bullosa Dystrophica / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D016896:Treatment Outcome
chemical_list: D024143:Collagen Type VII