Grant: Operating Grant

Rheumatoid arthritis and related inflammatory diseases collectively affect more than 16% of Canadians with an estimated socio-economic burden of $6 billion annually in Canada (www.publichealth.gc.ca). The symptoms associated with these debilitating diseases are the results of an underlying state of chronic inflammation. Current treatments for arthritis and related diseases directly inhibit critical molecules of the immune system. As a result these treatments often have unwanted side effects of making patients more susceptible to infections and sometimes the development of certain cancers. Therefore, there is an urgent need for new drugs that do not produce the negative side effects of the current therapies for controlling these diseases. We have shown that a group of small molecules known as innate defence regulator (IDR) peptides can suppress inflammation while maintaining the immune system's ability to control infections. This dual function of IDR peptides makes them attractive candidates as potential therapeutics for arthritis and related diseases. In our recent studies, we have shown that a IDR peptide can control arthritis in mice. We have now established the experimental tools and animal models that will allow us to more fully examine the activity of these peptides as a treatment for arthritis. In this project, we will study the biological effects of IDR peptides during the different stages of disease progression in a mouse model of arthritis. We will also establish how these peptides are able to suppress inflammation and control the disease process in different cell types relevant to arthritis. The results from this project will support the development of new IDR peptide therapeutics for arthritis, and will also identify new drug targets that can potentially be used to develop future anti-inflammatory therapeutics.