C3-targeted therapy in periodontal disease: moving closer to the clinic. Issue 10 (October 2021)

• Record Type: Journal Article
• Authors: Hajishengallis, George; Hasturk, Hatice; Lambris, John D.; Apatzidou, Danae A.; Belibasakis, Georgios N.; Bostanci, Nagihan; Corby, Patricia M.; Cutler, Christopher W.; D'Aiuto, Francesco; Hajishengallis, Evlambia; Huber-Lang, Markus; Ioannidou, Effie; Kajikawa, Tetsuhiro; Kantarci, Alpdogan; Korostoff, Jonathan M.; Kotsakis, Georgios A.; Maekawa, Tomoki; Mastellos, Dimitrios C.; Moutsopoulos, Niki M.; Myneni, Srinivas; Nagelberg, Richard; Nilsson, Bo; Papapanou, Panos N.; Papathanasiou, Evangelos; Potempa, Jan; Risitano, Antonio; Sahingur, S. Esra; Saito, Atsushi; Sculean, Anton; Stavropoulos, Andreas; Teles, Flavia R.; Tonetti, Maurizio; Yancopoulou, Despina;
• Is Part Of: Trends in immunology. Volume 42:Issue 10(2021)
• Page Start: 856
• Page End: 864
• Publication Date: 2021-10
• Subjects: Immunology -- Periodicals; 571.96
• DOI: 10.1016/j.it.2021.08.001
• Languages: English
• ISSNs: 1471-4906

Abstract

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. Highlights: Complement is a key contributor to immunosurveillance and homeostasis; however, when dysregulated or overactivated, complement can mediate pathological inflammation. Periodontitis is a prevalent chronic inflammatory disease of mammalian tissues that surround and support the teeth. It constitutes a significant healthcare and socioeconomic burden. Clinical studies have shown that complement is overactivated in periodontitis and that there is a correlation between periodontal inflammation and complement activation. Complement involvement in the pathogenesis of periodontitis was demonstrated in preclinical mouse and nonhuman primate studies, identifying C3 as a potential target of therapeutic intervention. A randomized, placebo-controlled, double-blind Phase IIa clinical trial showed that C3-targeted inhibition blocks gingival inflammation in patients with periodontal disease.