title: Inhibition of pre-existing natural periodontitis in non-human primates by a locally administered peptide inhibitor of complement C3.
abstract: OBJECTIVE
  Human periodontitis is associated with overactivation of complement, which is triggered by different mechanisms converging on C3, the central hub of the system. We assessed whether the C3 inhibitor Cp40 inhibits naturally occurring periodontitis in non-human primates (NHPs).
  
  
  METHODS
  Non-human primates with chronic periodontitis were intra-gingivally injected with Cp40 either once (5 animals) or three times (10 animals) weekly for 6 weeks followed by a 6-week follow-up period. Clinical periodontal examinations and collection of gingival crevicular fluid and biopsies of gingiva and bone were performed at baseline and during the study. A one-way repeated-measures anova was used for data analysis.
  
  
  RESULTS
  Whether administered once or three times weekly, Cp40 caused a significant reduction in clinical indices that measure periodontal inflammation (gingival index and bleeding on probing), tissue destruction (probing pocket depth and clinical attachment level) or tooth mobility. These clinical changes were associated with significantly reduced levels of pro-inflammatory mediators and decreased numbers of osteoclasts in bone biopsies. The protective effects of Cp40 persisted, albeit at reduced efficacy, for at least 6 weeks following drug discontinuation.
  
  
  CONCLUSIONS
  Cp40 inhibits pre-existing chronic periodontal inflammation and osteoclastogenesis in NHPs, suggesting a novel adjunctive anti-inflammatory therapy for treating human periodontitis.
authors.affiliation: Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Research Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Maekawa
authors.affiliation: College of Dentistry, Manila Central University, Caloocan City, Philippines.
authors.forename: Ruel A
authors.initials: RA
authors.lastname: Briones
authors.affiliation: Simian Conservation Breeding and Research Center (SICONBREC), Makati City, Philippines.
authors.forename: Ranillo R G
authors.initials: RR
authors.lastname: Resuello
authors.affiliation: Simian Conservation Breeding and Research Center (SICONBREC), Makati City, Philippines.
authors.forename: Joel V
authors.initials: JV
authors.lastname: Tuplano
authors.affiliation: Division of Pediatric Dentistry, Department of Preventive and Restorative Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Evlambia
authors.initials: E
authors.lastname: Hajishengallis
authors.affiliation: Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Kajikawa
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Sophia
authors.initials: S
authors.lastname: Koutsogiannaki
authors.affiliation: College of Dentistry, Manila Central University, Caloocan City, Philippines.
authors.forename: Cristina A G
authors.initials: CA
authors.lastname: Garcia
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ricklin
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
authors.affiliation: Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: George
authors.initials: G
authors.lastname: Hajishengallis
mesh_terms: D000818:Animals; D003176:Complement C3; D005883:Gingival Crevicular Fluid; D008252:Macaca fascicularis; D008297:Male; D010455:Peptides; D017622:Periodontal Attachment Loss / Q000188:drug therapy; D010512:Periodontal Index; D010514:Periodontal Pocket / Q000188:drug therapy; D010518:Periodontitis / Q000188:drug therapy*
chemical_list: D003176:Complement C3; D010455:Peptides
keywords: complement; compstatin; cytokines; inflammation; non-human primates; periodontitis