Grant: Operating Grant

Oral and stomach lining cells provide an important function by protecting hosts from infection caused by bacteria or their toxic products. Cells must join together to form a barrier that protects underlying tissues from this bacterial challenge. Periodontal disease and gastrointestinal (GI) tract infections are associated in part with disruption of this natural barrier. Previously we identified a class of enzymes that are increased in periodontal disease and, when inhibited by a family of existing drugs, the disease was diminished. This grant provides preliminary evidence that these drugs improve the barrier and has identified a possible mechanism by which this occurs. Specifically, we identified a cell surface-associated molecule that is released when cells are challenged by bacterial cellular factors and release of this molecule is associated with reduction of the barrier. The class of drugs that reduces these effects is commercially available and is clinically used to treat patients with Parkinson's disease. In our potential clinical application, we do not want drugs to be crossing to the brain if this is not required. We will therefore redevelop the drug so that it is no longer able to do this but will still protect oral and gut barrier function. Development of these modified drugs may prove to be a new and innovative approach to manage common oral and GI tract diseases.