期刊
TRENDS IN IMMUNOLOGY
卷 42, 期 10, 页码 856-864出版社
CELL PRESS
DOI: 10.1016/j.it.2021.08.001
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资金
- US National Institutes of Health [AI068730, AI030 040, DE015254, DE021685]
- European Commission [FP7-DIREK 602699]
- National Institutes of Health
Complement has a crucial role in periodontal disease, and targeting its central component C3 provides therapeutic benefits, potentially representing a novel approach for treating periodontitis.
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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