C3-targeted therapy in periodontal disease: moving closer to the clinic

Contributing authors

doi:10.1016/j.it.2021.08.001

C3-targeted therapy in periodontal disease: moving closer to the clinic

Contributing authors

College of Dental Medicine

Producción científica › revisión exhaustiva

30 Citas (Scopus)

Resumen

Complement plays a key role in immunosurveillance and homeostasis. When dysregulated or overactivated, complement can become a pathological effector, as seen in several inflammatory disorders, including periodontal disease. Recently, clinical correlative studies and preclinical mechanistic investigations have collectively demonstrated that complement is hyperactivated during periodontitis and that targeting its central component (C3) provides therapeutic benefit in nonhuman primates (NHPs). The preclinical efficacy of a C3-targeted drug candidate combined with excellent safety and pharmacokinetic profiles supported its use in a recent Phase IIa clinical study in which C3 inhibition resolved gingival inflammation in patients with periodontal disease. We posit that C3-targeted intervention might represent a novel and transformative host-modulation therapy meriting further investigation in Phase III clinical trials for the treatment of periodontitis.

Idioma original	English
Páginas (desde-hasta)	856-864
Número de páginas	9
Publicación	Trends in Immunology
Volumen	42
N.º	10
DOI	https://doi.org/10.1016/j.it.2021.08.001
Estado	Published - oct. 2021

Financiación

The cited preclinical complement studies were supported by grants from the US National Institutes of Health (AI068730, AI030040, DE015254, and DE021685), the European Commission (FP7-DIREKT 602699). This work was funded in part by the intramural program of the National Institutes of Health. The figures were generated using Biorender.com. G.H. H.H. and J.D.L. conceived and prepared the original draft and all authors contributed to the writing and/or editing of the final version of this Opinion article. J.D.L. is the founder of Amyndas Pharmaceuticals, which is developing complement inhibitors (including third-generation compstatin analogs such as AMY-101). J.D.L. is an inventor on patents or patent applications that describe the use of complement inhibitors for therapeutic purposes, some of which are developed by Amyndas Pharmaceuticals. J.D.L. and G.H. have a joint patent that describes the use of complement inhibitors for therapeutic purposes in periodontitis. J.D.L. is also the inventor of the compstatin technology licensed to Apellis Pharmaceuticals [i.e. 4(1MeW)7W/POT-4/APL-1 and PEGylated derivatives; e.g. APL-2/pegcetacoplan/Empaveli). The cited preclinical complement studies were supported by grants from the US National Institutes of Health ( AI068730 , AI030040 , DE015254, and DE021685 ), the European Commission ( FP7-DIREKT 602699 ). This work was funded in part by the intramural program of the National Institutes of Health . The figures were generated using Biorender.com .

Financiadores	Número del financiador
National Institutes of Health	AI068730, DE021685, DE015254
National Institute of Allergy and Infectious Diseases	N01AI030040
European Commission	APL-2/pegcetacoplan/Empaveli, 1MeW)7W/POT-4/APL-1, AMY-101, FP7-DIREKT 602699

ASJC Scopus Subject Areas

Immunology and Allergy
Immunology

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10.1016/j.it.2021.08.001

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title = "C3-targeted therapy in periodontal disease: moving closer to the clinic",

abstract = "Complement plays a key role in immunosurveillance and homeostasis. When dysregulated or overactivated, complement can become a pathological effector, as seen in several inflammatory disorders, including periodontal disease. Recently, clinical correlative studies and preclinical mechanistic investigations have collectively demonstrated that complement is hyperactivated during periodontitis and that targeting its central component (C3) provides therapeutic benefit in nonhuman primates (NHPs). The preclinical efficacy of a C3-targeted drug candidate combined with excellent safety and pharmacokinetic profiles supported its use in a recent Phase IIa clinical study in which C3 inhibition resolved gingival inflammation in patients with periodontal disease. We posit that C3-targeted intervention might represent a novel and transformative host-modulation therapy meriting further investigation in Phase III clinical trials for the treatment of periodontitis.",

author = "{Contributing authors} and George Hajishengallis and Hatice Hasturk and Lambris, {John D.} and Apatzidou, {Danae A.} and Belibasakis, {Georgios N.} and Nagihan Bostanci and Corby, {Patricia M.} and Cutler, {Christopher W.} and Francesco D'Aiuto and Evlambia Hajishengallis and Markus Huber-Lang and Effie Ioannidou and Tetsuhiro Kajikawa and Alpdogan Kantarci and Korostoff, {Jonathan M.} and Kotsakis, {Georgios A.} and Tomoki Maekawa and Mastellos, {Dimitrios C.} and Moutsopoulos, {Niki M.} and Srinivas Myneni and Richard Nagelberg and Bo Nilsson and Papapanou, {Panos N.} and Evangelos Papathanasiou and Jan Potempa and Antonio Risitano and Sahingur, {S. Esra} and Atsushi Saito and Anton Sculean and Andreas Stavropoulos and Teles, {Flavia R.} and Maurizio Tonetti and Despina Yancopoulou",

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AU - Apatzidou, Danae A.

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AU - D'Aiuto, Francesco

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AU - Ioannidou, Effie

AU - Kajikawa, Tetsuhiro

AU - Kantarci, Alpdogan

AU - Korostoff, Jonathan M.

AU - Kotsakis, Georgios A.

AU - Maekawa, Tomoki

AU - Mastellos, Dimitrios C.

AU - Moutsopoulos, Niki M.

AU - Myneni, Srinivas

AU - Nagelberg, Richard

AU - Nilsson, Bo

AU - Papapanou, Panos N.

AU - Papathanasiou, Evangelos

AU - Potempa, Jan

AU - Risitano, Antonio

AU - Sahingur, S. Esra

AU - Saito, Atsushi

AU - Sculean, Anton

AU - Stavropoulos, Andreas

AU - Teles, Flavia R.

AU - Tonetti, Maurizio

AU - Yancopoulou, Despina

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AB - Complement plays a key role in immunosurveillance and homeostasis. When dysregulated or overactivated, complement can become a pathological effector, as seen in several inflammatory disorders, including periodontal disease. Recently, clinical correlative studies and preclinical mechanistic investigations have collectively demonstrated that complement is hyperactivated during periodontitis and that targeting its central component (C3) provides therapeutic benefit in nonhuman primates (NHPs). The preclinical efficacy of a C3-targeted drug candidate combined with excellent safety and pharmacokinetic profiles supported its use in a recent Phase IIa clinical study in which C3 inhibition resolved gingival inflammation in patients with periodontal disease. We posit that C3-targeted intervention might represent a novel and transformative host-modulation therapy meriting further investigation in Phase III clinical trials for the treatment of periodontitis.

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C3-targeted therapy in periodontal disease: moving closer to the clinic

Resumen

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ASJC Scopus Subject Areas

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