title: Novel investigational agents for the treatment of scleroderma.
abstract: BACKGROUND
  The purpose of this article is to highlight novel therapies that are being used in scleroderma (SSc). Therapeutic interventions in SSc generally target at least one of three ongoing biological processes characteristic of the disease: vasculopathy, autoimmunity and tissue fibrosis. Treatment decisions in SSc are determined by the level of disease activity and the degree of specific organ involvement. Traditional therapy has primarily focused on organ-specific management without clear evidence of overall disease modification.
  
  
  METHODS
  The authors provide a review of a variety of agents, which are already used for other autoimmune diseases, that are now being used to treat active SSc skin or lung disease, including rituximab, tocilizumab and IVIG. Several agents studied in vitro and in animal models of fibrosis have shown promise, including bortezomib, LPA-1 antagonists, anti-CCN2 therapy, anti-IL-13 and thrombin antagonists. The authors also provide details on targeting intracellular molecular pathways and matricellular proteins, which is another novel area of investigation.
  
  
  CONCLUSIONS
  Combination therapy may be necessary to control the complex biological network active in SSc. Most of the current evidence that suggest benefit of these agents is based on small population studies. Ultimately well-designed clinical trials are required to define the role of these agents in treating SSc.
authors.affiliation: Johns Hopkins University, Medicine/Rheumatology , 55200 Eastern Avenue, MFL Center Tower, Suite 5300, Baltimore, MD 21224 , USA.
authors.forename: Zsuzsanna Hortobagyi
authors.initials: ZH
authors.lastname: McMahan
authors.forename: Fredrick M
authors.initials: FM
authors.lastname: Wigley
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000627:therapeutic use; D016207:Cytokines / Q000276:immunology; D015507:Drugs, Investigational / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000276:immunology
chemical_list: D002317:Cardiovascular Agents; D016207:Cytokines; D015507:Drugs, Investigational; D007155:Immunologic Factors; D036341:Intercellular Signaling Peptides and Proteins