MRC Technology has launched two new collaborations with Prof Mauro Perretti at the William Harvey Research Institute, Queen Mary University of London (QMUL). Both collaborations will exploit G-protein coupled receptors (GPCRs) identified as effectors of endogenous resolution.
The QMUL laboratory has pioneered the concept of studying the resolution of acute inflammation to identify pathways and mediators that can be exploited for controlling aberrant or uncontrolled inflammation, such as in vascular inflammation or chronic inflammation of the joint. The over-arching hypothesis is that therapeutics developed on the ‘Resolution of Inflammation’ concept will be burdened by a lower degree of side effects because they mimic the way our body naturally resolves inflammation.
The first collaboration will develop selective formyl peptide receptor 2 (FPR2) agonists for the treatment of ischaemia reperfusion injury. FPR2 is expressed by neutrophils, monocytes and leukocytes and is activated by both short-lived lipids (lipoxin A4, resolving D1) and longer lasting protein (Annexin A1) ligands. FPR2 is involved in the resolution phase of inflammation, and FPR2 activators could be used as a novel therapeutics for modulating ischaemia-reperfusion injury as a co-therapy with current approaches.
The second collaboration will develop positive allosteric modulators (PAMs) and agonists of melanocortin receptor type 3 (MC3) for treatment of joint disease. MC3 is expressed in the synovial tissue of RA patients, and is activated by melanocortin peptides, such as adrenocorticotropic hormone (ACTH) and melanocyte-stimulating hormone (MSH). MC3 modulates an endogenous anti-inflammation pathway. Hormones such as ACTH are therapeutically effective in rheumatoid and gouty arthritis, and exert potent protective effects in several models of inflammation, arthritis and tissue-injury. Several lines of evidence suggest that MC3 is an endogenous anti-inflammatory receptor for ACTH in joints and it is therefore a novel target for selective activators in chronic inflammatory joint disease.