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.

• Authors: George Hajishengallis, Hatice Hasturk, John D Lambris, Contributing authors
• Journal: Trends in immunology (Trends Immunol) Vol. 42 Issue 10 Pg. 856-864 (10 2021) ISSN: 1471-4981 [Electronic] England
• PMID: 34483038 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Published by Elsevier Ltd.

Chemical References

• Complement C3

Topics

• Animals
• Clinical Trial Protocols as Topic
• Clinical Trials, Phase III as Topic
• Complement C3
• Humans
• Periodontitis (drug therapy)