Breakthrough Therapy Designated Oral Drug Could Protect or Reverse COVID-19-Induced Heart Damage

“We exposed the bioengineered, stem-cell-derived heart tissue to COVID-19 patient blood and found it caused dysfunction even when the virus didn’t infect the tissue. These experiments revealed which inflammatory factors are potentially causing the cardiac problems. These factors activate bromodomain protein 4 in the heart, which we found was the key driver of cytokine storm damage,” said Associate Professor James Hudson, head of QIMR Berghofer’s Cardiac Bioengineering Research Group.

“We then used our mini heart organoids to screen several existing drugs that inhibit this protein and found they can prevent and reverse the damage. One of these was apabetalone, which was also effective at blocking the inflammatory response. Because it is already in Phase 3 clinical trials for treating cardiovascular disease, it could be available sooner to treat COVID-19 patients,” added Hudson.

The laboratory tests showed apabetalone also decreased the expression of the receptor protein ACE2, which is found on the cell surface and is used by the SARS-CoV-2 virus to infect cells. Apabetalone belongs to a new class of drugs that has been in clinical trials for cardiovascular disease for more than five years. It has received breakthrough therapy designation from the US Food and Drug Administration. Resverlogix initially planned to study apabetalone to improve clinical status in SARS-CoV-2 infected patients, but will now also examine if it can treat heart damage.

“Not only does apabetalone treatment reduce SARS-CoV-2 infection in cardiomyocytes, but it also prevents cardiac dysfunction induced by cytokine-storm,” said Donald McCaffrey, President and CEO of Resverlogix. “These findings showcase the unique dual-mechanism of apabetalone as a potential treatment for COVID-19 and provide strong support for human clinical trials.”

Related Links:
QIMR Berghofer Medical Research Institute
Resverlogix Corp.