Immuno-resolution: The Next Frontier for Treating Inflammatory Diseases

Uncontrolled inflammation is an important component of many chronic diseases, including arthritis, asthma, psoriasis, arteriosclerosis, and inflammatory bowel disease (IBD). Treatment of these diseases often utilizes anti-inflammatory agents that block steps in the inflammatory response and suppress the immune system. Unfortunately, such agents are only partially effective and can lead to undesirable side effects such as immunosuppression and an increased risk of infection.

However, a fundamentally new approach to treating chronic inflammatory disease that utilizes the body’s natural healing processes has emerged based on the discovery that inflammation is actively regulated by naturally occurring bioactive lipids that are already present in humans, known as specialized pro-resolving mediators (SPMs). SPMs have demonstrated potent immunoresolving effects in a variety of inflammatory disease models at extremely low doses, and offer a new approach to treating chronic inflammatory disease based on actively promoting the resolution of inflammation.

Immuno-resolving therapies offer several therapeutic advantages over traditional anti-inflammatory therapies. First, they are not expected to have the same side effects as immunosuppressive therapies, like increased risk of infection. In fact, some SPMs have been shown to increase the body’s ability to combat infection. Second, the long-term complications of chronic inflammatory diseases are often the result of collateral tissue damage caused by inflammation. In addition to initiating the resolution of inflammation, SPMs have been shown to actively promote tissue repair and regeneration. Thus, immunoresolving therapies may prevent new inflammation-associated tissue damage from occurring while simultaneously initiating and accelerating the healing of damaged tissue.

Thetis’ TP-317 candidate for treatment of IBD delivers therapeutic levels of Resolvin E1, an SPM that has been shown in preclinical models of various inflammatory diseases, including ulcerative colitis, to promote the resolution of inflammation and accelerate tissue repair. These effects also have been demonstrated with oral administration of TP-317 at very low doses. This agent represents a fundamentally new disease-modifying approach to IBD treatment and is a pioneering step towards the introduction of immunoresolving therapies for clinical use.