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Review
. 2020 Jun 19;22(8):42.
doi: 10.1007/s11926-020-00918-3.

Current and Potential New Targets in Systemic Sclerosis Therapy: a New Hope

Monique Hinchcliff  1 , Steven O'Reilly  2
Affiliations
Review

Current and Potential New Targets in Systemic Sclerosis Therapy: a New Hope

Monique Hinchcliff et al. Curr Rheumatol Rep. .

Abstract

Purpose of review: Systemic sclerosis (SSc) is an autoimmune connective tissue disease in which there is an activation of fibroblast to a myofibroblast that secretes huge amounts of extracellular matrix. Currently, no treatment exists that modifies the fibrosis elements and new therapeutic targets are badly needed. This review examines the current state of treatments and emerging therapeutics.

Recent findings: Nintedanib was found to significantly reduce the rate of decline in SSc associated FVC, although it has no benefit on skin fibrosis. New cannabinoid receptor2 agonist has shown superb effects in phase II and results in phase III are anticipated. Other targets are currently being tested in clinical trials and new targets that are yet to be tested are increasing in the SSc literature. Nintedanib is now licenced for SSc interstitial lung disease but this does not modify the skin fibrosis. Current ongoing trials will determine the role of various targets. New targets are emerging as we gain a deeper understanding of disease pathogenesis.

Keywords: Cytokines; Janus kinases; Pathogenesis; STAT3; Systemic sclerosis.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Mechanism of action of nintedanib in lung fibrosis in SSc. Nintedanib work by binding to the ATP binding pocket FGF, PDGF and VEGF receptors resulting in blockade of the autophosphorylation of these receptors and subsequent downstream signalling pathways. This approach blocks pro-fibrotic and proliferative pathways downstream of the receptors stimulation which includes Src and Ras (not shown). This multiplicity of the targets may underpin is therapeutic efficacy. FGF fibroblast growth factor, PDGF platelet-derived growth factor, VEGF vascular endothelial growth factor
See this image and copyright information in PMC

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