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Safety and Efficacy of the Complement Inhibitor AMY-101 in a Natural Model of Periodontitis in Non-human Primates
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 previ...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577415/ https://www.ncbi.nlm.nih.gov/pubmed/28879212 http://dx.doi.org/10.1016/j.omtm.2017.08.001 |
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author | Kajikawa, Tetsuhiro Briones, Ruel A. Resuello, Ranillo R.G. Tuplano, Joel V. Reis, Edimara S. Hajishengallis, Evlambia Garcia, Cristina A.G. Yancopoulou, Despina Lambris, John D. Hajishengallis, George |
author_facet | Kajikawa, Tetsuhiro Briones, Ruel A. Resuello, Ranillo R.G. Tuplano, Joel V. Reis, Edimara S. Hajishengallis, Evlambia Garcia, Cristina A.G. Yancopoulou, Despina Lambris, John D. Hajishengallis, George |
author_sort | Kajikawa, Tetsuhiro |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5577415 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-55774152017-09-06 Safety and Efficacy of the Complement Inhibitor AMY-101 in a Natural Model of Periodontitis in Non-human Primates Kajikawa, Tetsuhiro Briones, Ruel A. Resuello, Ranillo R.G. Tuplano, Joel V. Reis, Edimara S. Hajishengallis, Evlambia Garcia, Cristina A.G. Yancopoulou, Despina Lambris, John D. Hajishengallis, George Mol Ther Methods Clin Dev Original Article 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. American Society of Gene & Cell Therapy 2017-08-18 /pmc/articles/PMC5577415/ /pubmed/28879212 http://dx.doi.org/10.1016/j.omtm.2017.08.001 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Kajikawa, Tetsuhiro Briones, Ruel A. Resuello, Ranillo R.G. Tuplano, Joel V. Reis, Edimara S. Hajishengallis, Evlambia Garcia, Cristina A.G. Yancopoulou, Despina Lambris, John D. Hajishengallis, George Safety and Efficacy of the Complement Inhibitor AMY-101 in a Natural Model of Periodontitis in Non-human Primates |
title | Safety and Efficacy of the Complement Inhibitor AMY-101 in a Natural Model of Periodontitis in Non-human Primates |
title_full | Safety and Efficacy of the Complement Inhibitor AMY-101 in a Natural Model of Periodontitis in Non-human Primates |
title_fullStr | Safety and Efficacy of the Complement Inhibitor AMY-101 in a Natural Model of Periodontitis in Non-human Primates |
title_full_unstemmed | Safety and Efficacy of the Complement Inhibitor AMY-101 in a Natural Model of Periodontitis in Non-human Primates |
title_short | Safety and Efficacy of the Complement Inhibitor AMY-101 in a Natural Model of Periodontitis in Non-human Primates |
title_sort | safety and efficacy of the complement inhibitor amy-101 in a natural model of periodontitis in non-human primates |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577415/ https://www.ncbi.nlm.nih.gov/pubmed/28879212 http://dx.doi.org/10.1016/j.omtm.2017.08.001 |
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