Ischemia reperfusion injury occurs in a broad range of conditions where blood flow has been temporarily occluded or impeded and results in acute inflammation, irreversible tissue damage, scar formation, and loss of tissue functionality. DecImmune's therapeutic programs capitalize on the pioneering discovery by its founders of an innate immune pathway that initiates the tissue-damaging immune and inflammatory cascade following vascular injury produced by ischemia.

Specifically, they identified a highly conserved self antigen, non-muscle myosin heavy chain II on hypoxic vascular endothelial cells and a specific natural antibody (IgM) that recognizes a short segment called N2. The recognition event activates the lectin pathway of the complement system and the release of the anaphylatoxins, C3a and C5a, and activates mast cells underlying the vascular endothelium. In more than 25 peer-reviewed publications, including studies in models of cardiovascular injury, shock, wound/trauma, second degree burns, stroke, and plastic surgery they have validated the N2 pathway as the dominant pathway leading to complement activation and resulting tissue damage (see diagram).

Innate Immune Pathway for Ischemia Induced Injury

Reperfusion of ischemic tissues induces release of an epitope (N2) within the cytoplasmic protein non-muscle myosin heavy chain II (NMHC-II) that activates the innate immune system. Recognition of the N2 epitope activates the lectin pathway of the complement system, leading to acute inflammation and tissue damage.

This research includes studies demonstrating that an otherwise non-pathogenic antibody becomes pathogenic in the setting of ischemia DecImmune is developing both peptide and antibody therapeutics that inhibit N2 IgM binding, to block the initiating events of the cascade and potentially reduce tissue damage, accelerate healing and improve outcomes by leaving more tissue functionally intact. The therapeutic candidates have potential to be applied to a range of conditions including myocardial infarction, stroke, burns, wound trauma and plastic surgery.