Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)—a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. No effective therapies are available. Based on the findings that TGF-beta activity is elevated in injured RDEB skin, Nystrom and colleagues targeted TGF-beta activity with losartan in RDEB mice. Long-term treatment with losartan reduced TGF-beta signaling in chronically injured forepaws and halted fibrosis and subsequent fusion of the digits. Losartan reduced inflammation and diminished TNF-alfa and IL-6 expression in injured forepaws. Collectively, the data argue that RDEB fibrosis is a consequence of a cascade encompassing tissue damage, TGF-beta-mediated inflammation, and matrix remodeling. The authors concluded that inhibition of TGF-beta activity limits these unwanted outcomes and thereby ameliorates the disease phenotype.
Posted by Nicola Brunetti-Pierri, MD