Format

Send to

Choose Destination
Mol Ther Methods Clin Dev. 2017 Aug 18;6:207-215. doi: 10.1016/j.omtm.2017.08.001. eCollection 2017 Sep 15.

Safety and Efficacy of the Complement Inhibitor AMY-101 in a Natural Model of Periodontitis in Non-human Primates.

Author information

1
University of Pennsylvania, School of Dental Medicine, Department of Microbiology, Philadelphia, PA 19104, USA.
2
Manila Central University, College of Dentistry, 1400 Caloocan City, Metro Manila, Philippines.
3
Simian Conservation Breeding and Research Center (SICONBREC), Makati City, Philippines.
4
University of Pennsylvania Perelman School of Medicine, Department of Pathology and Laboratory Medicine, Philadelphia, PA 19104, USA.
5
University of Pennsylvania, School of Dental Medicine, Department of Preventive and Restorative Sciences, Division of Pediatric Dentistry, Philadelphia, PA 19104, USA.
6
Amyndas Pharmaceuticals, 16675 Glyfada, Greece.

Abstract

Periodontitis is a chronic inflammatory disease associated with overactivation of the complement system. Recent preclinical studies suggest that host-modulation therapies may contribute to effective treatment of human periodontitis, which may lead to loss of teeth and function if untreated. We previously showed that locally administered AMY-101 (Cp40), a peptidic inhibitor of the central complement component C3, can inhibit naturally occurring periodontitis in non-human primates (NHPs) when given once a week. This study was undertaken to determine the local safety of increasing doses of the drug as well as its efficacy when given at a reduced frequency or after systemic administration. Our findings have determined a local dose of AMY-101 (0.1 mg/site) that is free of local irritation and effective when given once every 3 weeks. Moreover, a daily subcutaneous dose of AMY-101 (4 mg/kg bodyweight) was protective against NHP periodontitis, suggesting that patients treated for systemic disorders (e.g., paroxysmal nocturnal hemoglobinuria) can additionally benefit in terms of improved periodontal condition. In summary, AMY-101 appears to be a promising candidate drug for the adjunctive treatment of human periodontitis, a notion that merits investigation in human clinical trials.

KEYWORDS:

AMY-101; complement; compstatin; inflammation; non-human primates; periodontitis

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center