TY - JOUR
T1 - Safety and Efficacy of the Complement Inhibitor AMY-101 in a Natural Model of Periodontitis in Non-human Primates
AU - Kajikawa, Tetsuhiro
AU - Briones, Ruel A.
AU - Resuello, Ranillo R.G.
AU - Tuplano, Joel V.
AU - Reis, Edimara S.
AU - Hajishengallis, Evlambia
AU - Garcia, Cristina A.G.
AU - Yancopoulou, Despina
AU - Lambris, John D.
AU - Hajishengallis, George
N1 - Funding Information:
This work was supported by grants from the NIH ( AI068730 and AI030040 to J.D.L. and DE015254 , DE021685 , and DE024716 to G.H.) and the European Commission ( FP7-DIREKT 602699 to J.D.L.).
Publisher Copyright:
© 2017 The Authors
PY - 2017/9/15
Y1 - 2017/9/15
N2 - 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.
AB - 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.
KW - AMY-101
KW - complement
KW - compstatin
KW - inflammation
KW - non-human primates
KW - periodontitis
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U2 - 10.1016/j.omtm.2017.08.001
DO - 10.1016/j.omtm.2017.08.001
M3 - Article
AN - SCOPUS:85029306974
SN - 2329-0501
VL - 6
SP - 207
EP - 215
JO - Molecular Therapy - Methods and Clinical Development
JF - Molecular Therapy - Methods and Clinical Development
ER -
