Brisbane: In a move that could help revolutionise how drugs for heart-related diseases are developed in the future, a group of Australian scientists recently conducted the first-ever screening of potential heart regeneration drugs by using bioengineered human heart muscle.
The four-year study was published in the journal ‘Cell Stem Cell’. It was led by researchers from QIMR Berghofer Medical Research Institute, the Murdoch Children’s Research Institute and the University of Melbourne, in collaboration with researchers from global biopharmaceutical company AstraZeneca.
The researchers used thousands of miniature heart muscles that were grown in the lab to eliminate compounds that did not work effectively or were toxic.
The lead author of the study, James Hudson, stated that the study also identified two potential drug candidates that may help regenerate damaged heart tissue without negative side effects on heart function.
“Currently potential new drugs are tested on heart cells or in mice but those tests don’t always accurately replicate the effects on human hearts,” Hudson said.
According to the study author, 90 per cent of the drugs that enter clinical trials show very promising results in the laboratory, but either don’t end up working for the patients or do not progress due to some side effects.
The study used thousands of miniature hurt muscles that grew in the laboratory and that beat and behaved like human hearts.
These mini heart muscles had similar properties to a functioning human heart. They also seemed to respond to drugs in a similar way to the organ.
AstraZeneca had previously identified potential new drug targets after testing about 5,000 compounds and shared more than 100 compounds with the Australian researchers for further testing in the mini-heart muscles.
Co-lead author, Enzo Porrello, said they were able to identify two compounds that may help repair the heart.
“Using the mini heart muscles in a dish we were able to eliminate many compounds that didn’t work effectively or were damaging or toxic, and we ended up finding two potential new drug candidates that may help regenerate damaged heart tissue,” he said.
The study also showed that heart muscle would only regenerate if the drug treatment could turn on specific metabolic pathways – something that hadn’t been shown before.
“It’s very early days, and there are years of testing ahead, but our research provides hope of finding therapeutics that could regenerate disease-damaged hearts,” Porrello added.
Hudson highlighted that the screening model also had the potential to make drug testing cheaper, quicker, easier and more accurate for the patients.
“We can make hundreds of heart muscles in the lab each week and use them to discover treatments that may be beneficial for patients with heart failure, thereby reducing our reliance on using mice and keeping testing costs down,” he said.
“Our next step is to work with AstraZeneca to improve the compounds so that they can be taken forward into pre-clinical testing,” Hudson concluded.