title: Complement inhibition in pre-clinical models of periodontitis and prospects for clinical application.
abstract: 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.
authors.affiliation: University of Pennsylvania, Penn Dental Medicine, Department of Microbiology, Philadelphia, PA 19104, USA. Electronic address: geoh@upenn.edu.
authors.forename: George
authors.initials: G
authors.lastname: Hajishengallis
authors.affiliation: University of Pennsylvania, Penn Dental Medicine, Department of Preventive and Restorative Sciences, Division of Pediatric Dentistry, Philadelphia, PA 19104, USA.
authors.forename: Evlambia
authors.initials: E
authors.lastname: Hajishengallis
authors.affiliation: University of Pennsylvania, Penn Dental Medicine, Department of Microbiology, Philadelphia, PA 19104, USA.
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Kajikawa
authors.affiliation: University of Pennsylvania, Penn Dental Medicine, Department of Microbiology, Philadelphia, PA 19104, USA.
authors.forename: Baomei
authors.initials: B
authors.lastname: Wang
authors.affiliation: Amyndas Pharmaceuticals, Glyfada 16675, Greece.
authors.forename: Despina
authors.initials: D
authors.lastname: Yancopoulou
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ricklin
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
mesh_terms: D000818:Animals; D003176:Complement C3 / Q000378:metabolism; D003182:Complement C5 / Q000378:metabolism; D051056:Complement Inactivating Agents / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D064806:Dysbiosis / Q000276:immunology / Q000628:therapy*; D006801:Humans; D009055:Mouth / Q000276:immunology* / Q000382:microbiology; D010518:Periodontitis / Q000276:immunology / Q000628:therapy*; D011323:Primates; D011728:Pyridones / Q000627:therapeutic use*; D044087:Receptor, Anaphylatoxin C5a / Q000378:metabolism
chemical_list: D003176:Complement C3; D003182:Complement C5; D051056:Complement Inactivating Agents; D011728:Pyridones; D044087:Receptor, Anaphylatoxin C5a; C098211:1-(ethan-1-ol)-2-methyl-3-hydroxypyridin-4-one
keywords: C3; Complement; Compstatin cp40; Inflammation; Periodontitis; Primate models; Therapeutics