The body's immune system monitors infection or damage to our bodies. It uses special sensors to detect microbes or products of damaged tissues. Inflammasomes are an important family of such sensors. They become active following the sensing of damage and they drive the production of two important signals, the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, which act to wake up the inflammatory response in our bodies.
Inflammation normally leads to repair to damaged tissue. However, if inflammation becomes chronic, all kinds of inflammatory diseases can occur. There are several inflammasomes, but the most well studied and understood is called NLRP3. The NLRP3 inflammasome has been shown to be overactive in many inflammatory diseases, including gout, osteoarthritis, atherosclerosis and neurological disorders such as Alzheimer’s and Parkinson’s disease.
Clinically used anti-inflammatories drugs include biologic therapeutics that target the main product of the NLRP3 inflammasome, IL-1, such as recombinant IL-1 receptor antagonist anakinra (Kineret), the neutralizing IL-1β antibody canakinumab (Ilaris) and the decoy IL-1 receptor rilonacept (Arcalyst). Canakinumab has recently been shown to have pronounced clinically protective effects in cardiovascular disease, cancer and arthritis, highlighting the potential value of a small molecule inhibitor of NLRP3 which will prevent IL-1β production.
Our mission at Inflazome is to identify and develop potent, first-in-class, small molecule NLRP3 inhibitors as treatments of a broad range of inflammatory diseases.