Repurposing BTK inhibitors as anti-inflammatory drugs in cardiovascular disease.
- 1 November 2018 to 31 March 2019
- Awards: Pump-priming Awards
There is an unmet need for new medicines for the treatment of cardiovascular disease, especially drugs that target macrophage inflammation in atherosclerosis. One potential source of new anti-inflammatory drugs is repurposing medicines currently used in oncology.
Ibrutinib (imbruvica) is a low molecular weight non-competitive inhibitor of Bruton’s tyrosine kinase (BTK) kinase activity that is used in the treatment of leukaemia.
Gareth Purvis has shown that ibrutinib has tissue protective effects in pre-clinical models of type-2 diabetes. Work in the Greaves Lab has shown ibrutinib reduces macrophage NF-KB and inflammasome activation and hence reduces inflammatory cytokine production. In addition we have shown that oral delivery of ibrutinib inhibits inflammatory cell recruitment in a murine models of acute inflammation.
We will publish our novel findings and then use that paper to apply for new funding streams to take BTK inhibitors into translational studies for diseases characterised by chronic macrophage activation.