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Scientists use thousands of miniature hearts to test potential new drugs

Research News
Published: 
Friday, March 29, 2019 - 9:02am

Image credit: Associate Professor James Hudson

Australian scientists have conducted the first ever screening of potential heart regeneration drugs using bioengineered human heart muscle – a move that could revolutionise how heart drugs are developed in the future.

The four-year study has been published today 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.

Lead author and head of QIMR Berghofer’s Organoid Research Laboratory, Associate Professor James Hudson, said 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,” Associate Professor Hudson said.

“About 90 per cent of drugs that enter clinical trials show very promising results in the laboratory, but either don’t end up working in patients or do not progress due to side effects.

“Our study used thousands of miniature heart muscles that we grew in the lab and that beat and behaved like a human heart.

“These mini heart muscles have similar properties to a functioning human heart and they seem 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 from the Murdoch Children’s Research Institute and The University of Melbourne 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.”

Associate Professor Hudson said the screening model also had the potential to make drug testing cheaper, quicker, easier and more accurate.

“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.

“Our next step is to work with AstraZeneca to improve the compounds so that they can be taken forward into pre-clinical testing.”

The study was funded by QIMR Berghofer, the Murdoch Children’s Research Institute, The University of Melbourne, The University of Sydney, NHMRC, Heart Foundation, Stem Cells Australia and The Royal Children’s Hospital Foundation.

Media Contacts:

QIMR Berghofer: Gail Burke, 0427 179 216 or gail.burke@qimrberghofer.edu.au

Murdoch Children’s Research Institute: Bridie Byrne, 0403 664 416 or bridie.byrne@mcri.edu.au