Grant: Project Grant

Inflammatory bowel disease (IBD) is a term that groups together chronic inflammatory diseases of the digestive tract, notably Crohn's disease and ulcerative colitis. It is projected that IBD will affect about 1% of our country's population by 2030. IBD typically arises in a patient's gastrointestinal tract as a result of the impact and interplay of environmental factors, genetic predisposition and the nature as well as the composition of their gut microbiota. These factors explain in part the multifactorial nature of IBD and why no cure presently exists. Patients are typically treated for their symptoms (chronic inflammation of the gut) with general anti-inflammatory drugs. More recently, biologics such as anti-TNF alpha antibodies have proven to provide more focused and effective anti-inflammatory responses for treating IBD. In either case, all IBD treatments cause broad immuno suppression and consequently come with adverse effects in patients such as their enhanced susceptibility to infections. As biologics are now becoming the first line of treatment for many autoimmune and inflammatory diseases, there is a need to focus their action to the site of inflammatory, in the case of IBD, to the gastrointestinal tract. We propose to design and construct biologics that will accumulate in the gut of IBD patients to locally reduce inflammation while minimizing the dosage needed and their overall systemic impact in patients. Experimentally, we plan to express, characterize and test our targeted biologics in mouse models displaying IBD-like inflammatory responses. The impact of our research program will be the development of a simple, rapid assembly strategy of anti-inflammatory biologics to guide them to the gut in order to locally treat IBD patients with less side effects.