Mark V. Dahl, MD
Promising results suggest systemic protein therapy with type VII collagen might help restore anchoring fibril formation and dermal–epidermal adherence in patients with recessive dystrophic epidermolysis bullosa.
Can people genetically unable to synthesize a protein use it if injected? Specifically, can injection of type VII collagen (C-VII) help patients with recessive dystrophic epidermolysis bullosa (RDEB) who lack this protein? Previously, these researchers injected C-VII in a mouse model of RDEB, where, perhaps surprisingly, it was promptly incorporated into the basement membrane zone. Injections into human, organotypic, constructed RDEB-equivalent skin lacking C-VII that had been transplanted onto immunocompromised mice were similarly successful.
Systemic protein therapy has been primarily employed in systemic diseases such as hemophilia or lysosomal storage disorders. Woodley and others wondered if intravenously injected recombinant C-VII (rC-VII) would move from plasma into the skin wounds of patients with RDEB and restore C-VII expression and function there. Athymic wounded nude mice received rC-VII, which did indeed home to skin wound sites at the dermal-epidermal junction in a dose-dependent fashion. C-VII protein could still be detected 8 weeks later, showing durability. No C-VII was detected in unwounded skin or in other organs. No adverse effects were seen. Next, they transplanted skin from C-VII knockout mice (which had no C-VII or anchoring fibers in skin) onto athymic nude mice. Again, injection of rC-VII stopped dermal-epidermal separation. Electron microscopy showed the engrafted skin of C-VII-injected mice developed anchoring fibers composed of C-VII.
Citation(s):
Woodley DT et al. Intravenously injected recombinant human type VII collagen homes to skin wounds and restores skin integrity of dystrophic epidermolysis bullosa. J Invest Dermatol 2013 Jul; 133:1910.
Hovnanian A. Systemic protein therapy for recessive dystrophic epidermolysis bullosa: How far are we from clinical translation? J Invest Dermatol 2013 Jul; 133:1719.
