title: Preclinical and translational research to discover potentially effective antifibrotic therapies in systemic sclerosis.
abstract: OBJECTIVE
  To discuss the strategies for preclinical and early clinical characterization of targeted antifibrotic therapies in order to optimize the probability of positive results in later stage clinical trials.
  
  
  RESULTS
  There is a high unmet clinical need for effective antifibrotic therapies in systemic sclerosis (SSc), and in parallel a rapid development in the identification of potential molecular targets in preclinical research. Herein, we discuss the strategies for the improvement of preclinical and early clinical trials. These strategies include identification and characterization of molecular targets for therapy in vitro, selection of relevant parameters in translational animal models, confirmation of target activation in human SSc, analysis of successful target coverage after drug exposure in human SSc, and conduct of biomarker-driven proof-of-concept studies as a bridge between animal studies and Phase IIB/III studies with clinical endpoints.
  
  
  CONCLUSIONS
  These strategies could increase the possibility to develop successful drugs against the fibrotic manifestations of SSc.
authors.affiliation: aDepartment of Rheumatology, University Hospital Zurich, Zurich, Switzerland bAmgen Inc., Thousand Oaks, California, USA.
authors.forename: Suzana
authors.initials: S
authors.lastname: Jordan
authors.forename: James
authors.initials: J
authors.lastname: Chung
authors.forename: Oliver
authors.initials: O
authors.lastname: Distler
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D015195:Drug Design; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods*; D012595:Scleroderma, Systemic / Q000188:drug therapy*; D057170:Translational Research, Biomedical / Q000379:methods; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers