Mini-hearts made from stem cells reveal how COVID-19 causes heart damage, leading to drug treatment trials.

In severe cases of COVID-19, out-of-control inflammation rampages through the body damaging tissues and organs such as the heart but, thanks to Brisbane researcher Associate Professor James Hudson, we may be on track to prevent or even reverse that harm.

James grew thousands of functioning mini-hearts from stem cells, which he and his colleagues used to track down the specific inflammatory pathways causing the damage by exposing the heart organoids to blood serum from COVID patients.

This was a huge scientific effort, involving James’ team at QIMR Berghofer, and collaborators at the University of Sydney, Murdoch Children’s Research Institute, The Peter Doherty Institute for Infection and Immunity, Monash University, and companies Resverlogix and Dynomics.

“We then used our mini-heart organoids to screen several existing drugs and discovered ones that can prevent and reverse the damage,” James explains.

Based on this Australian research, the Canadian biotechnology company Resverlogix is now running a phase II clinical trial of the drug Apabetalone to see if it can improve the outcome of hospitalised COVID patients.

The drug was able to be rapidly repurposed straight to phase II trials as it was already in phase III human trials for treating cardiovascular disease. It recently received breakthrough therapy designation from the US regulator, the Food and Drug Administration.

“It’s a tablet, so if someone gets COVID-19 they can go to hospital and start taking the drug. It could potentially stop people from dying or prevent some of the side effects of the disease. There is also evidence that it may act on multiple organs,” James says.

“It could be transformational. It’s a small molecule that’s easy and cheap to produce, and stable at room temperature – that makes it much more accessible to everyone.”

James’ work is a direct application of the research for which he won a 2019 Metcalf Prize for Stem Cell Research. Even then his vision was to mass-produce mini-hearts from stem cells to provide living tissue to rapidly test the potential of hundreds of existing and new drugs to treat different diseases.

James is also working with regular collaborator and fellow Metcalf Prize winner Enzo Porrello from Murdoch Children’s Research Institute.

Their research has benefitted from $390,000 in funding from the Medical Research Future Fund to establish human stem cell-based models of COVID-19 infection, to better understand the disease and screen potential treatments.

James says winning the Metcalf Prize helped raise his profile and gave valuable recognition of his work, which helped attract further funding and support, positioning him to rise to the challenge when a global pandemic struck.

His message to up-and-coming researchers considering entering the Metcalf Prizes: “It’s a great initiative. It raises your profile and helps you network with senior stem cell scientists. You should go for it!”

Read more about James’ COVID research on the QIMR Berghofer website. Read the Cell paper, publishing the research.