Preclinical data outlining the mechanisms of three proteins shown to restore heart function following acute myocardial infarction (heart attack) presented at AHA
Forcefield Therapeutics (“Forcefield”) Ltd, a pioneer of best-in-class therapeutics to protect heart function by arresting the loss of cardiomyocytes following myocardial infarction, has presented positive preclinical data on three proteins identified by the FunSel platform which have potential to preserve heart function following a heart attack.The paper, Novel Recombinant Cardioprotective Factors Against Myocardial Infarction Selected in vivo from an AAV Secretome Library, was presented on Sunday November 6th at the 2022 Scientific Sessions of American Heart Association (AHA) in Chicago by Dr Mateusz Tomczyk, Research Associate at King’s College London.
The paper presented preclinical data outlining the mechanisms of three proteins identified by FunSel, Forcefield’s protein ‘search engine’. FunSel is ‘gene agnostic’: unconstrained by genetics and does not rely on knowledge of which factor is causing a disease. It allows ‘functional selection’ of therapeutic factors for disease phenotype correction. FunSel contains a library of thousands of AAV vectors encoding secreted proteins.
Results presented at AHA show that, after two rounds of iterative selection in mice, the three proteins identified by FunSel preserved cardiomyocyte viability, sustained cardiac function and prevented pathological remodelling. In both neonatal cardiomyocytes and adult hearts, all three factors reduced apoptosis and induced protective macro-autophagy. In particular, Chrdl1 exerted its protective activity by binding and inhibiting extracellular bone morphogenetic protein 4 (BMP4), which resulted in protection against cardiomyocyte death and induction of autophagy in cardiomyocytes after myocardial infarction. In addition, it was found that two variants optimised for clinical development demonstrate preliminary efficacy when administered using the anticipated clinical route and time of administration in a myocardial infarction model.
The work developing FunSel originated at the International Centre for Genetic Engineering and Biology (ICGEB) and the University of Trieste, Italy. It has been further developed by Mauro Giacca, Professor of Cardiovascular Sciences at King’s College London and co-founder of Forcefield Therapeutics and supported by the British Heart Foundation. Forcefield Therapeutics, a pioneer of best-in-class therapeutics to retain heart function via protection of cardiomyocytes was launched in 2022 backed by leading healthcare investor Syncona and is undertaking the development work to enable clinical trials in patients in the future.
Professor Mauro Giacca commented:
“While early stage, these data support our conviction in the importance of the three proteins we have identified. These can be administered immediately after a heart attack to minimise cardiac damage and therefore have the potential to revolutionise treatments for patients at risk of heart failure.
These findings reveal a method for the systematic, in vivo selection of tissue protective factors and disclose novel potential cardiac therapeutics, and we’re very excited about their potential.”