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Targeted Therapy in Systemic Sclerosis.

Murray Baron1

  • 1Chief Division of Rheumatology, Jewish General Hospital, Montreal, Quebec, Canada; and Professor of Medicine, McGill University, Montreal, Quebec, Canada.

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|November 9, 2016
PubMed
Summary
This summary is machine-generated.

New targeted therapies for systemic sclerosis (SSc) are emerging, focusing on key cells and pathways like B cells and transforming growth factor-beta. Clinical trials are investigating drugs such as rituximab and fresolimumab for SSc treatment.

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Area of Science:

  • Rheumatology and Immunology
  • Translational Medicine

Background:

  • Systemic sclerosis (SSc), or scleroderma, is a complex autoimmune disease characterized by fibrosis and vascular abnormalities.
  • Understanding the underlying pathophysiology of SSc has paved the way for developing targeted therapeutic strategies.
  • While patient-specific treatments are still developing, recent insights into disease pathogenesis have guided the selection of novel drug candidates.

Approach:

  • Investigating the role of B cells in SSc pathogenesis, leading to trials of rituximab (anti-CD20 antibody).
  • Targeting transforming growth factor-beta (TGF-β), a key mediator of collagen synthesis, with fresolimumab.
  • Exploring the impact of interleukin-6 (IL-6) in SSc pathogenesis, prompting trials of tocilizumab.
  • Examining the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) pathway, with trials of riociguat.
  • Assessing the role of tyrosine kinases (TKs) in fibrogenesis and vascular remodeling, leading to trials of nintedanib.

Key Points:

  • Rituximab targets B cells implicated in SSc.
  • Fresolimumab neutralizes TGF-β to inhibit collagen production.
  • Tocilizumab targets IL-6, a cytokine involved in SSc pathogenesis.
  • Riociguat modulates the sGC pathway.
  • Nintedanib inhibits multiple tyrosine kinases involved in SSc processes.

Conclusions:

  • Several targeted therapies are under investigation for systemic sclerosis, addressing distinct cellular and molecular pathways.
  • These trials represent a shift towards mechanism-based treatments for SSc, moving beyond generalized immunosuppression.
  • Further research and clinical trials are crucial to establish the efficacy and safety of these novel SSc therapies.