Simvastatin Prevents and Reverses Depigmentation in a Mouse Model of Vitiligo Priti Agarwal1, Mehdi Rashighi1, Kingsley I Essien1, Jillian M Richmond1, Louise Randall2, Hamidreza Pazoki-Toroudi3, Christopher A Hunter4 and John Harris1 Journal of Investigative Dermatology, 18 December 2014 1 Division of Dermatology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA 2Department of Medicine, The University of Melbourne, Melbourne Victoria, Australia 3Department of Physiology, Iran University of Medical Sciences, Tehran, Iran 4Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA Abstract Vitiligo is a common autoimmune disease of the skin that results in disfiguring white spots. There are no FDA-approved treatments, and current treatments are time-consuming, expensive, and have low efficacy. We sought to identify new treatments for vitiligo, and first considered repurposed medications because of the availability of safety data and expedited regulatory approval. We previously reported that the IFN-γ-induced chemokine CXCL10 is expressed in lesional skin from vitiligo patients, and that it is critical for the progression and maintenance of depigmentation in our mouse model of vitiligo. We hypothesized that targeting IFN-γ signaling might be an effective new treatment strategy. STAT1 activation is required for IFN-γ signaling and recent studies revealed that simvastatin, an FDA-approved cholesterol-lowering medication, inhibited STAT1 activation in vitro. Therefore, we hypothesized that simvastatin may be an effective treatment for vitiligo. We found that simvastatin both prevented and reversed depigmentation in our mouse model of vitiligo, and reduced the number of infiltrating autoreactive CD8+ T cells in the skin. Treatment of melanocyte-specific, CD8+ T cells in vitro decreased proliferation and IFN-γ production, suggesting additional effects of simvastatin directly on T cells. Based on these data, simvastatin may be a safe, targeted treatment option for patients with vitiligo.
Posted on: Mon, 22 Dec 2014 16:33:35 +0000
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