Friday, May 23, 2025
5/23/2025
Novel therapy to prevent alveolar bone loss in severe periodontitis - Novel therapy to prevent alveolar bone loss in severe periodontitis Abstract Periodontal disease affects almost half of US adults 30 years and older. More advanced disease, periodontitis, leads to retraction of the gums from the teeth, with loss of alveolar bone, and ultimately loss of teeth. A key step in progression of periodontitis involves the loss of alveolar bone that provides the underlying support for the tooth. This process is mediated by bone-degrading osteoclasts (OC). Osteoclast activation by inflammatory mediators disrupts bone homeostasis, leading to loss of bone mass. OC differentiation from OC progenitor cells (OCP) is modulated by a cascade of integrated signaling culminating in stimulation by RANKL that ultimately leads to fusion of OCP to form the active, multinucleated OC. While multiple fusogens, including the dendritic cell-specific transmembrane protein (DC-STAMP) and CD9, are recognized, recent data suggest a pivotal role for OC-stimulatory transmembrane protein (OC-STAMP). OC-STAMP knock-out mice exhibit diminished alveolar bone loss in a standard ligature-induced model of periodontitis. Unlike anti-DC-STAMP, anti- OC-STAMP down-regulates expression of CD9. These studies of osteoclastogenesis involving OC-STAMP suggest a potential therapeutic intervention for periodontitis using an anti-OC-STAMP monoclonal antibody. Proof-of-concept work utilized a murine-specific anti-OC-STAMP murine monoclonal antibody. During this Phase 1 project, we will identify and evaluate a panel of human anti-human OC-STAMP monoclonal antibodies. A lead antibody will be identified using a ligature-induced periodontitis model in a human OC-STAMP knock-in mouse model. This work will produce a novel therapeutic to slow or even potentially halt loss of alveolar bone and teeth in severe periodontitis.
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