title: Simvastatin prevents and reverses depigmentation in a mouse model of vitiligo.
abstract: Vitiligo is a common autoimmune disease of the skin that results in disfiguring white spots. There are no Food and Drug Administration (FDA)-approved treatments, and current treatments are time-consuming, expensive, and of 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. Activation of signal transducer and activator of transcription 1 (STAT1) 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.
authors.affiliation: Division of Dermatology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Priti
authors.initials: P
authors.lastname: Agarwal
authors.affiliation: Division of Dermatology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Rashighi
authors.affiliation: Division of Dermatology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Kingsley I
authors.initials: KI
authors.lastname: Essien
authors.affiliation: Division of Dermatology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Jillian M
authors.initials: JM
authors.lastname: Richmond
authors.affiliation: Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Louise
authors.initials: L
authors.lastname: Randall
authors.affiliation: Department of Physiology, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Pazoki-Toroudi
authors.affiliation: Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hunter
authors.affiliation: Division of Dermatology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA. Electronic address: john.harris@umassmed.edu.
authors.forename: John E
authors.initials: JE
authors.lastname: Harris
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D049109:Cell Proliferation; D054357:Chemokine CXCL10 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007371:Interferon-gamma / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D010858:Pigmentation; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D019821:Simvastatin / Q000627:therapeutic use*; D012867:Skin / Q000378:metabolism; D012880:Skin Pigmentation; D014820:Vitiligo / Q000188:drug therapy*
chemical_list: D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D007371:Interferon-gamma; D019821:Simvastatin