Simvastatin prevents and reverses depigmentation in a mouse model of vitiligo
Division of Dermatology; Department of Medicine
Dermatology | Skin and Connective Tissue Diseases
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-gamma-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-gamma signaling might be an effective new treatment strategy. Activation of signal transducer and activator of transcription 1 (STAT1) is required for IFN-gamma 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-gamma 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.
DOI of Published Version
J Invest Dermatol. 2015 Apr;135(4):1080-8. doi: 10.1038/jid.2014.529. Epub 2014 Dec 18. Link to article on publisher's site
The Journal of investigative dermatology
Agarwal, Priti; Rashighi, Medhi; Essien, Kingsley I.; Richmond, Jillian M.; Randall, Louise; Pazoki-Toroudi, Hamidreza; Hunter, Christopher A.; and Harris, John E., "Simvastatin prevents and reverses depigmentation in a mouse model of vitiligo" (2015). Dermatology Publications and Presentations. 83.