Targeting the NLRP3 inflammasome for the treatment of inflammatory diseases
The NLRP3 inflammasome has emerged as a key mediator of damaging inflammation in many chronic diseases which are a large, and increasing, burden on public health. Atherosclerosis, Alzheimer’s disease, Parkinson’s disease, asthma, liver disease, and arthritis are all associated with NLRP3 activation making it an attractive therapeutic target. I will describe our characterisation of MCC950, a potent and specific small molecule inhibitor of NLRP3, from its initial discovery to the determination of its mechanism of action. NLRP3 inhibitors are currently being evaluated in early clinical trials and I will discuss the potential therapeutic application of this new class of anti-inflammatory therapies.
Dr Rebecca Coll is a Lecturer in Immunobiology and Group Leader at the Wellcome-Wolfson Institute for Experimental Medicine at Queen’s University Belfast, UK. Dr Coll started her independent research group in 2019 with a focus on characterising inflammasome biology in human health and disease. Dr Coll developed her expertise in inflammatory signalling pathways in the innate immune system through her PhD (awarded 2013) with Prof. Luke O’Neill (Trinity College Dublin) and her postdoctoral training with Prof Kate Schroder (Institute for Molecular Bioscience, University of Queensland), which was supported by a UQ Postdoctoral Research-Industry Fellowship. A particular focus has been small-molecule inhibitors of the NLRP3 inflammasome and this cross-disciplinary research has been extremely successful, generating nine publications including landmark studies on the NLRP3 inhibitor MCC950 (Coll et al., Nature Medicine, 2015; Coll et al. Nature Chemical Biology, 2019). Dr Coll is a co-inventor on a granted patent and two patent applications pertaining to NLRP3 inhibitors that were licensed to Inflazome Ltd. In 2020, Inflazome was purchased by Roche for $620M. Dr Coll’s international expertise in inflammasome inhibitors has been recognised by her Research Australia Discovery award (2016) and an ICIS Regeneron New Investigator Award for Excellence in Cytokine & Interferon Research (2021).