Grant: Operating Grant

Preventing tissue damage in arthritis: Validation of a new approach. For the 4 million canadians suffering from arthritis, non-steroidal anti-inflammatory drugs (NSAIDs) are their most prescribed class of medication. These compounds block swelling and pain, in part through inhibition of an enzyme termed cyclooxygenase, responsible for the generation of prostaglandins. On the other hand, the use of NSAIDs is associated with severe side effects ranging from gastric ulcers to kidney malfunctions, and to death in extreme cases. Moreover, NSAIDs do not slow down progression of chronic inflammatory diseases as they do not stop the cells responsible for bone and cartilage destruction. Recent in vitro observations have justified a strong interest for the development of cAMP elevating agents as anti-inflammatory drugs. Indeed, cAMP appears to be a strong anti-inflammatory signal in leukocytes, cells which are held responsible for tissue degradation in arthritis. We plan to test this approach in vivo with a selection of compounds known to increase intracellular cAMP levels, such as prostaglandin E2, in experimental models of arthritis and of inflammation. Results of this project may immediately find clinical potential as a treatment for slowing down disease progression.