Innovative antifibrotic therapies in systemic sclerosis

Curr Opin Rheumatol. 2012 May;24(3):274-80. doi: 10.1097/BOR.0b013e3283524b9a.

Abstract

Purpose of review: Fibrosis is a key feature of systemic sclerosis (SSc) and arises from excessive release of collagens by pathologically activated fibroblasts. Affecting the skin and many internal organs, fibrosis represents a major cause for the high morbidity and mortality in SSc. So far, effective therapies to treat fibrosis in SSc and other fibrotic diseases are not available in clinical routine. Nevertheless, promising antifibrotic agents are emerging from translational studies with some having already entered clinical trials.

Recent findings: In this review, we focus on recent advances in the development of antifibrotic treatment strategies in SSc. We have selected for targeted therapeutic approaches that have proven high efficacy and tolerability in preclinical fibrosis models of SSc and/or are already in clinical evaluation. Applying these criteria, we discuss a large repertory of candidate antifibrotic therapies that block inflammatory pathways, inhibit profibrotic growth factors, modulate epigenetic signaling, and interfere with morphogenic pathways.

Summary: Many antifibrotic candidate therapies have proven efficacy and tolerability in preclinical models of SSc. So far, early clinical studies have tested only few of these agents. Besides discovering novel molecular treatment strategies, SSc research will now have to translate its findings into clinical practice.

Publication types

  • Review

MeSH terms

  • Epigenesis, Genetic / drug effects
  • Fibrosis / drug therapy
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Molecular Targeted Therapy / methods*
  • Morphogenesis
  • Scleroderma, Systemic / drug therapy*
  • Scleroderma, Systemic / pathology
  • Signal Transduction / drug effects
  • Transforming Growth Factor beta / antagonists & inhibitors

Substances

  • Immunosuppressive Agents
  • Transforming Growth Factor beta