Complement-Dependent Mechanisms and Interventions in Periodontal Disease

Front Immunol. 2019 Mar 12;10:406. doi: 10.3389/fimmu.2019.00406. eCollection 2019.

Abstract

Periodontitis is a prevalent inflammatory disease that leads to the destruction of the tooth-supporting tissues. Current therapies are not effective for all patients and this oral disease continues to be a significant public health and economic burden. Central to periodontal disease pathogenesis is a reciprocally reinforced interplay between microbial dysbiosis and destructive inflammation, suggesting the potential relevance of host-modulation therapies. This review summarizes and discusses clinical observations and pre-clinical intervention studies that collectively suggest that complement is hyperactivated in periodontitis and that its inhibition provides a therapeutic benefit. Specifically, interception of the complement cascade at its central component, C3, using a locally administered small peptidic compound (Cp40/AMY-101) protected non-human primates from induced or naturally occurring periodontitis. These studies indicate that C3-targeted intervention merits investigation as an adjunctive treatment of periodontal disease in humans.

Keywords: AMY-101; C3; complement; compstatin Cp40; inflammation; periodontitis; primate models; therapeutics.

Publication types

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

MeSH terms

  • Animals
  • Complement Activation / drug effects*
  • Complement C3 / antagonists & inhibitors*
  • Complement C3 / immunology
  • Dysbiosis / microbiology
  • Humans
  • Macaca fascicularis
  • Mice
  • Periodontitis / immunology*
  • Periodontitis / pathology
  • Periodontitis / therapy*
  • Pyridones / pharmacology*

Substances

  • Complement C3
  • Pyridones
  • 1-(ethan-1-ol)-2-methyl-3-hydroxypyridin-4-one