A Novel Anti-Inflammatory Approach to Treat Hypertension

2019 Vanguard Grant

Years funded: 2020-2022

Hypertension is the major risk factor for many cardiovascular diseases, and its incidence is predicted to continue to grow, thus developing novel pharmacological therapeutic approaches are essential to address the shortcomings of current therapies. Despite current knowledge that the immune system plays an important role in hypertension disease progression and end-organ damage, this is one therapeutic avenue that reminds to be explored. Thus, targeting receptor family integral to the inflammatory response, such as formyl peptide receptors (FPRs), may offer a new therapeutic approach to attenuate hypertension and the associated inflammatory state.

The applicant has identified a small-molecule FPR activator (Cmpd17b) that provides superior cardio-protection than the conventional activator, providing new insights on drug discovery strategy for cardiovascular disease. This paradigm-shifting discovery has been patented, and published in highly prestigious scientific journal. In addition, this work has also attracted significant media attention, and led to the recent establishment of a spin-off start-up biotech company (Limulus Therapeutics Pty Ltd

In this proposal, we will evaluate the capacity of our prototype small molecule (Cmpd17b) to improve blood vessel function and to prevent vascular re-modelling (scaring) in hypertension. Experiments will extend from cell based studies to well validated pre-clinical models of hypertension. The project will test the hypothesis that our prototype drug candidate will improve vascular function and protect against vascular injury in hypertension. We will examine the ability of FPR activator to lower blood pressure, and limit consequential blood vessel inflammation and re-modelling. The proposed studies will provide critical insight into the therapeutic potential of biased FPR agonists. We anticipate that this study will ultimately facilitate development of exciting new ways to treat hypertension, that affects 300,000 Australians.