Efficacy of Rapamycin in Scleroderma: A Case Study

• Type of Material: Article
• Authors: Levi Fried, Emory University; Robert S. Kirsner, Emory University; Sulochana S. Bhandarkar, Emory University; Jack Arbiser, Emory University
• Language: English
• Date: 2008-12-18
• Publisher: Mary Ann Liebert
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © Mary Ann Liebert, Inc.
• Final Published Version (URL): http://online.liebertpub.com/doi/abs/10.1089/lrb.2008.1006
• Title of Journal or Parent Work: Lymphatic Research and Biology
• ISSN: 1539-6851
• Volume: 6
• Issue: 3-4
• Start Page: 217
• End Page: 219
• Grant/Funding Information: JLA was supported by the grant RO1 AR47901 and P30 AR42687 Emory Skin Disease Research Core Center Grant from the National Institutes of Health, a Veterans Administration Hospital Merit Award.
• Research Categories: Health Sciences, General; Biology, General

Abstract

Scleroderma is a common autoimmune disorder with no effective therapy. Current concepts of scleroderma include the hypothesis that scleroderma results from excess conversion of endothelial cells to fibroblast like cells, called endothelial mesenchymal transformation. This process is thought to be mediated by cytokines including transforming growth factor beta (TGFb), which causes increased collagen synthesis, resulting in fibrosis, the hallmark of the disease. In vitro studies have hypothesized that rapamycin may be of benefit in scleroderma due to antagonism of collagen synthesis. Given that rapamycin has antiangiogenic activities, inhibits wound healing, and prevents the synthesis of collagen in vivo, we tried rapamycin in a patient with scleroderma. We observed rapid improvement in skin stiffness and mobility. Our results provide the rationale for larger clinical trials of rapamycin in scleroderma and other fibrotic disorders.