Complement inhibition in pre-clinical models of periodontitis and prospects for clinical application

Semin Immunol. 2016 Jun;28(3):285-91. doi: 10.1016/j.smim.2016.03.006. Epub 2016 Mar 24.


Periodontitis is a dysbiotic inflammatory disease leading to the destruction of the tooth-supporting tissues. Current therapies are not always effective and this prevalent oral disease continues to be a significant health and economic burden. Early clinical studies have associated periodontitis with elevated complement activity. Consistently, subsequent genetic and pharmacological studies in rodents have implicated the central complement component C3 and downstream signaling pathways in periodontal host-microbe interactions that promote dysbiosis and inflammatory bone loss. This review discusses these mechanistic advances and moreover focuses on the compstatin family of C3 inhibitors as a novel approach to treat periodontitis. In this regard, local application of the current lead analog Cp40 was recently shown to block both inducible and naturally occurring periodontitis in non-human primates. These promising results from non-human primate studies and the parallel development of Cp40 for clinical use highlight the feasibility for developing an adjunctive, C3-targeted therapy for human periodontitis.

Keywords: C3; Complement; Compstatin cp40; Inflammation; Periodontitis; Primate models; Therapeutics.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Complement C3 / metabolism
  • Complement C5 / metabolism
  • Complement Inactivating Agents / therapeutic use*
  • Drug Evaluation, Preclinical
  • Dysbiosis / immunology
  • Dysbiosis / therapy*
  • Humans
  • Mouth / immunology*
  • Mouth / microbiology
  • Periodontitis / immunology
  • Periodontitis / therapy*
  • Primates
  • Pyridones / therapeutic use*
  • Receptor, Anaphylatoxin C5a / metabolism


  • Complement C3
  • Complement C5
  • Complement Inactivating Agents
  • Pyridones
  • Receptor, Anaphylatoxin C5a
  • 1-(ethan-1-ol)-2-methyl-3-hydroxypyridin-4-one