Future treatments in systemic sclerosis
Article first published online: 24 JAN 2010
© 2010 Japanese Dermatological Association
The Journal of Dermatology
Special Issue: Systemic Sclerosis (pages 1-84)
Volume 37, Issue 1, pages 54–70, January 2010
How to Cite
ASANO, Y. (2010), Future treatments in systemic sclerosis. The Journal of Dermatology, 37: 54–70. doi: 10.1111/j.1346-8138.2009.00758.x
- Issue published online: 24 JAN 2010
- Article first published online: 24 JAN 2010
- Received 19 October 2009; accepted 9 November 2009.
- immune dysfunction;
- new treatments;
Systemic sclerosis (SSc) is an autoimmune disorder with clinical manifestations resulting from immune activation, fibrosis development and damage of small blood vessels. Although there have been no established treatments for SSc, lots of new treatments targeting organ and pathogenesis are in the process of development. Transforming growth factor (TGF)-β is a major cytokine involved in the pathogenesis of fibrosis in SSc. The blockade of cell surface molecules capable of activating latent TGF-β, blockade of ligand by the pan-isoform-specific antibody, soluble TGF-β receptors and a recombinant latency associated peptide, as well as inhibitors for ALK5 and Smad3 are the potential strategies to abolish the pathological activation of TGF-β signaling in SSc fibroblasts. Besides TGF-β, connective tissue growth factor (CTGF)/CCN2, platelet-derived growth factor (PDGF) and endothelin-1 are the candidates for the new therapeutic targets. As for immune dysfunction in SSc, i.v. immunoglobulin infusion, stem cell transplantation and B-cell depletion are potential new therapies under or awaiting a randomized, double-blind, placebo-controlled trial, although their efficacies are still controversial. Phosphodiesterase-5 inhibitors, endothelin receptor antagonists and inhibitors for serotonin signaling are the new therapeutic targets for Raynaud’s phenomenon, digital ulceration and pulmonary arterial hypertension in SSc. Imatinib mesylate may be a novel new therapy for fibrosis and vasculopathy in SSc because it reverses the expression levels of Fli1, which is a transcription factor downregulated in SSc through an epigenetic mechanism and is likely to be involved in the development of fibrosis and vasculopathy in this disease. Potential therapeutic targets other than those described above are also reviewed.