C3-targeted therapy in periodontal disease: moving closer to the clinic
George Hajishengallis, Hatice Hasturk, John D Lambris, Contributing authors, Danae A Apatzidou, Georgios N Belibasakis, Nagihan Bostanci, Patricia M Corby, Christopher W Cutler, Francesco D'Aiuto, Evlambia Hajishengallis, Markus Huber-Lang, Effie Ioannidou, Tetsuhiro Kajikawa, Alpdogan Kantarci, Jonathan M Korostoff, Georgios A Kotsakis, Tomoki Maekawa, Dimitrios C Mastellos, Niki M Moutsopoulos, Srinivas Myneni, Richard Nagelberg, Bo Nilsson, Panos N Papapanou, Evangelos Papathanasiou, Jan Potempa, Antonio Risitano, S Esra Sahingur, Atsushi Saito, Anton Sculean, Andreas Stavropoulos, Flavia R Teles, Maurizio Tonetti, Despina Yancopoulou, George Hajishengallis, Hatice Hasturk, John D Lambris, Contributing authors, Danae A Apatzidou, Georgios N Belibasakis, Nagihan Bostanci, Patricia M Corby, Christopher W Cutler, Francesco D'Aiuto, Evlambia Hajishengallis, Markus Huber-Lang, Effie Ioannidou, Tetsuhiro Kajikawa, Alpdogan Kantarci, Jonathan M Korostoff, Georgios A Kotsakis, Tomoki Maekawa, Dimitrios C Mastellos, Niki M Moutsopoulos, Srinivas Myneni, Richard Nagelberg, Bo Nilsson, Panos N Papapanou, Evangelos Papathanasiou, Jan Potempa, Antonio Risitano, S Esra Sahingur, Atsushi Saito, Anton Sculean, Andreas Stavropoulos, Flavia R Teles, Maurizio Tonetti, Despina Yancopoulou
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.
Trial registration: ClinicalTrials.gov NCT03316521 NCT03694444.
Conflict of interest statement
Declaration of interests 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).
Published by Elsevier Ltd.
Figures
Source: PubMed