Periodontitis, a prevalent oral inflammatory disease associated with increased risk of systemic comorbidities, continues to be a significant worldwide public health and economic burden. The complement system is hyperactivated in periodontitis and is involved both in the dysbiotic transformation of the periodontal microbiome and the destructive inflammation that causes loss of periodontal bone. Targeting the central complement component C3 with the drug AMY-101 provided therapeutic benefit in nonhuman primates (NHP) with periodontal disease. The preclinical efficacy of this C3-targeted drug combined with its excellent safety and pharmacokinetic profiles supported the use of AMY-101 in a recent Phase IIa clinical study, in which C3 inhibition resolved gingival inflammation in patients with periodontal disease. These studies by the Hajishengallis and Lambris groups and their collaborators were discussed at the 9th Annual Congress of the European Society for Translational Medicine on Immunotherapeutics. (October 3-5, 2022). Based on the available evidence, C3-targeted intervention represents a novel and transformative treatment of human periodontitis and other complement-driven oral pathologies such as peri-implantitis.
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