Human periodontal (gum) disease (i.e., gingivitis, and periodontitis - a more severe form of gingivitis) is the result of infections associated with specific oral bacteria below the gum lines. Chronic inflammatory periodontitis is the leading cause of tooth loss in adults (prevalence, >80 percent worldwide). Approximately $15 billion dollars per year are spent on its diagnosis, professional cleaning and treatment including the replacement of affected teeth in the United States. Recently, severe periodontal disease has been shown to be associated with an increased risk for coronary heart disease, stroke, bacterial pneumonia, diabetes and undesired pregnant outcomes. Conventional periodontal treatment relies on mechanical debridement of the affected teeth and gums by scaling, root planning and surgeries, sometimes combined with antibiotic usage, which suffers from nonspecific removal of the target microorganisms, high costs, time consuming, emergence of antibiotic resistance strains, re-infection of the gums etc. Therefore, human periodontal disease is a significant health and healthcare issue. In the current application, the applicant proposed to develop a new generation of neutralizing human single-chain Fv monoclonal antibodies (called: scFv-MoAbs) against a recently defined critical microbial target involved in human periodontitis, CagE homologue: a death-inducing protein of an etiological human periodontal pathogen, Actinobacillus actinomycetemcmomitans, from infected gum tissues. Importantly, the resulting neutralizing monoclonal antibodies will be tested in a """"""""humanized"""""""" mouse model established by the applicant to validate the efficacy of the scFv-MoAbs being assessed before approaching human clinical studies. This combined new technology and specifically targeted approach by applying scFv-MoAbs to modulate or treat periodontal infections, if successful, will likely to become the new therapy for gum diseases and infections in the 21st century. Therefore, the patients' periodontal health will be improved and, eventually, this new treatment modality will also alleviate the chronic or/and long-term exposure of periodontal infections to systemic complications or risks; thereby, reducing the health-care burden and the associated socio-economical costs. ? ?
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