In vivo demonstration of potency to improve impaired efferocytosis and control inflammation related to Systemic Lupus Erythematosus (SLE)

Challenge: Lupus is a chronic autoimmune disease in which the body immune system attacks its own tissues, causing inflammation and tissue damage. Systemic lupus erythematosus (SLE) is the most common type. It affects 1/1000 individuals, mostly women. In healthy people, more than 50 billion cells die daily as part of a normal biological mechanism: replacing old cells by new ones. Dead cells are rapidly eliminated to prevent toxic cellular debris. In SLE, the natural mechanism of dead cell elimination is impaired, leading to cell debris accumulation in organs, which in turn induces an inappropriate immune reaction and inflammation that damage these organs. It is likely that compounds designed to improve clearance of cell debris and to control aberrant inflammation in SLE would be of significant help to patients. Anti-inflammatory therapies are currently used to treat SLE but do not eliminate pain and have significant side-effects. It is imperative to develop newer approaches for SLE treatment targeting not only the inappropriate inflammation, but also the broken dead cell removal system.

Solution: Specialized pro-resolving mediators (SPM) compounds are recently identified natural mediators responsible for controlling inflammation in humans. These compounds also improve death cell debris removal. Administration of SPM compounds may improve SLE symptoms and even treat the disease. The research team will study the benefits of a proprietary chemical analog of SPM on SLE symptoms using a novel mouse model that recapitulates SLE in humans.

Expected achievements/Impact: The demonstration that an SPM analog  is effective in reducing SLE symptoms in a new mouse model will open the way for its development as an SLE therapeutic drug. It will further position the Quebec City-based SPM Therapeutics to become a leader in inflammation/pain resolution drug development and licensing.