Miniature hearts used to test potential new drugs

Wednesday, 10 April, 2019

Miniature hearts used to test potential new drugs

Australian scientists have conducted what is claimed to be 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 was led by researchers from QIMR Berghofer Medical Research Institute, the Murdoch Children’s Research Institute and the University of Melbourne, in collaboration with global biopharmaceutical company AstraZeneca. The results were published in the journal Cell Stem Cell.

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

“About 90% 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.”

The green is the cardiomyocytes (muscle cells) and the red is the proliferating cells (growing cells) after treatment with one of the compounds. Image credit: Richard Mills, QIMR Berghofer.

AstraZeneca had previously identified potential new drug targets after testing about 5000 compounds, and shared more than 100 compounds with the Australian researchers for further testing in the mini heart muscles. The scientists said they were able to identify two compounds that may help regenerate damaged heart tissue without negative side effects on heart function.

“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,” said co-lead author Assoc Prof Enzo Porrello, from the Murdoch Children’s Research Institute and the University of Melbourne.

“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.”

Assoc Prof Hudson said the screening model also has 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,” he said.

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

Top image credit: © Schonertagen

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