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Future treatments in systemic sclerosis.
- Source :
-
The Journal of dermatology [J Dermatol] 2010 Jan; Vol. 37 (1), pp. 54-70. - Publication Year :
- 2010
-
Abstract
- 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)-beta is a major cytokine involved in the pathogenesis of fibrosis in SSc. The blockade of cell surface molecules capable of activating latent TGF-beta, blockade of ligand by the pan-isoform-specific antibody, soluble TGF-beta 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-beta signaling in SSc fibroblasts. Besides TGF-beta, 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.
- Subjects :
- Animals
Autoimmune Diseases physiopathology
B-Lymphocytes immunology
Benzamides
Connective Tissue Growth Factor antagonists & inhibitors
Connective Tissue Growth Factor immunology
Endothelin Receptor Antagonists
Endothelin-1 antagonists & inhibitors
Endothelin-1 immunology
Humans
Imatinib Mesylate
Immunoglobulins therapeutic use
Mice
Phosphodiesterase 5 Inhibitors
Piperazines therapeutic use
Platelet-Derived Growth Factor antagonists & inhibitors
Platelet-Derived Growth Factor immunology
Pyrimidines therapeutic use
Randomized Controlled Trials as Topic
Receptors, Transforming Growth Factor beta antagonists & inhibitors
Receptors, Transforming Growth Factor beta immunology
Scleroderma, Systemic physiopathology
Selective Serotonin Reuptake Inhibitors therapeutic use
Smad3 Protein antagonists & inhibitors
Smad3 Protein immunology
Transforming Growth Factor beta antagonists & inhibitors
Transforming Growth Factor beta immunology
Autoimmune Diseases drug therapy
Autoimmune Diseases immunology
Scleroderma, Systemic drug therapy
Scleroderma, Systemic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1346-8138
- Volume :
- 37
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 20175840
- Full Text :
- https://doi.org/10.1111/j.1346-8138.2009.00758.x