Key result
AZD8601 injection increases myocardial VEGF-A protein levels in explanted human hearts.
Why the study?
This proof-of-concept study aimed to evaluate the utility of testing novel therapies on explanted human recipient hearts using ex situ machine perfusion.
Ex situ perfusion of explanted human hearts provides a viable experimental model for testing novel cardiovascular therapeutics like AZD8601.
Supports ex vivo human heart models for testing novel agents; leaves open clinical translation of AZD8601.
Background Explanted hearts from recipients undergoing cardiac transplantation may be utilised as a human model of cardiomyopathy. Ex-situ perfusion of hearts allows control of the physiological and biochemical conditions of perfusion. AZD8601 is a novel modRNA for VEGF-A that was shown to be safe in a Phase IIa clinical trial – the EPICCURE trial. This proof-of-concept study aimed to demonstrate the potential utility of testing novel therapies on explanted recipient hearts using ex situ machine perfusion. Methods In order to ascertain the expression of VEGF-A in a human model of cardiomyopathy, AZD8601 was injected at high- and low-dose into the mid-myocardium of the left ventricle of human hearts explanted at the time of cardiac transplantation and perfused on the m0rgan, a novel, normothermic organ perfusion machine. Hearts were perfused ex situ for 6 hours. After which, injection sites were biopsied and divided into subendocardium, mid-myocardium and sub-epicardial myocardium. Immuno-analysis was performed to assess levels of VEGF-A protein. Results There were elevated levels of VEGF-A protein in the subendocardium and mid-myocardium of injection sites which received AZD8601 . Low-dose and high-dose AZD8601 resulted in a significantly higher concentration of VEGF-A protein in the myocardium. Conclusions This study builds on the EPICCURE study, a phase IIa clinical trial which demonstrated safety of this mRNA in patients undergoing coronary artery bypass grafting. This study provides a novel model of diseased human heart for experimental studies utilising ex situ heart perfusion.
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Louca et al. (2025) studied Cardiomyopathy. AZD8601 was evaluated on Levels of VEGF-A protein. Injection of AZD8601 into explanted human hearts perfused ex situ resulted in significantly higher concentrations of VEGF-A protein in the myocardium.
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