Grant: Project Grant

The elegance of 'helminth (worm) therapy' is it requires only that the host mount a natural response to a helminth (one that has been fine-tuned over millennia), and consequently concomitant disease can be suppressed. Thus, helminth therapy is presented as a novel approach to inflammatory disease that can be used to individualize therapy to a patient. Inflammatory bowel disease (IBD) affects ~270,000 Canadians; Crohn's disease and ulcerative colitis are devastating diseases, physiologically and psychologically, for which there is no cure and current treatments, while improving, are far from perfect. Using mouse model systems, we have shown that infection with a tapeworm parasite reduces the severity of inflammation in the colon. Our preliminary data show that the protective effect of infection with the worm is lost if mice are co-treated with antibiotics. The antibiotics do not affect the parasite, clearly indicating that disruption of the normal composition of the bacteria in the colon negates the protective effect of infection with the worm. Using cutting-edge methods and model systems established in my laboratory, a series of experiments are proposed to assess the worm-bacteria-host relationship. The goal is to define the precise requirements for the mechanism of action of helminth therapy in the suppression of colitis that can ultimately be applied to patients. The proposed research advances a personalized-medicine paradigm for IBD where a therapeutic helminth may be prescribed that is matched to the genetic, immunological and gut-bacteria characteristics of the patient.