A potentially life-saving treatment for heart attack victims has been discovered from a very unlikely source – the venom of one of the world’s deadliest spiders. A drug candidate developed from a molecule found in the venom of the Fraser Island (K’gari) funnel web spider can prevent damage caused by a heart attack and extend the life of donor hearts used for organ transplants.
The discovery was made by a team led by Professor Peter Macdonald from the Victor Chang Cardiac Research Institute and Dr Nathan Palpant and Professor Glenn King from The University of Queensland (UQ).
Victor Chang Cardiac Research Institute’s Professor Macdonald said this incredible result had been decades in the making:
“This will not only help the hundreds of thousands of people who have a heart attack every year around the world, it could also increase the number and quality of donor hearts, which will give hope to those waiting on the transplant list”
Dr Palpant, from UQ’s Institute for Molecular Bioscience (IMB), said the drug candidate worked by stopping a ‘death signal’ sent from the heart in the wake of an attack.
“After a heart attack, blood flow to the heart is reduced, resulting in a lack of oxygen to heart muscle,” Dr Palpant said.
“The lack of oxygen causes the cell environment to become acidic, which combine to send a message for heart cells to die.”
“Despite decades of research, no one has been able to develop a drug that stops this death signal in heart cells, which is one of the reasons why heart disease continues to be the leading cause of death in the world.”
Dr Palpant tested the drug candidate, a protein called Hi1a, using beating human heart cells exposed to heart attack stresses to see if the drug improved their survival.
“The Hi1a protein from spider venom blocks acid-sensing ion channels in the heart, so the death message is blocked, cell death is reduced, and we see improved heart cell survival.”
There are currently no drugs in clinical use that prevent the damage caused by heart attacks.
Professor Macdonald, who is also a senior cardiologist at St Vincent’s Hospital in Sydney, added: “The survival of heart cells is vital in heart transplants — treating hearts with Hi1a and reducing cell death will increase how far the heart can be transported and improve the likelihood of a successful transplant.
“Usually, if the donor heart has stopped beating for more than 30 minutes before retrieval, the heart can’t be used - even if we can buy an extra 10 minutes, that could make the difference between someone having a heart and someone missing out. For people who are literally on death’s door, this could be life-changing.”
The discovery builds on earlier work by Professor King, who identified a small protein in the venom of the Fraser Island (K’gari) funnel-web spider that was shown to markedly improve recovery from stroke.
“We discovered this small protein, Hi1a, amazingly reduces damage to the brain even when it is given up to eight hours after stroke onset,” Professor King said.
“It made sense to also test Hi1a on heart cells, because like the brain, the heart is one of the most sensitive organs in the body to the loss of blood flow and lack of oxygen.
“For heart attack victims, our vision for the future is that Hi1a could be administered by first responders in the ambulance, which would really change the health outcomes of heart disease.”
“This is particularly important in rural and remote parts of Australia where patients and treating hospitals can be long distances apart – and when every second counts.”
This could also help for the transfer of donor hearts for cardiac transplantation – allowing donor hearts to be transported over longer distances and therefore increasing the network of available donors and recipients.
The protein has been tested in human heart cells, and the team is aiming for human clinical trials for both stroke and heart disease to begin within two to three years.
Cardiothoracic Research Fellow Dr Sarah Scheuer is a PhD Candidate and part of the research team from the Victor Change Cardiac Research Institute.
She says their research initially just looked just at the effect of venom but moved down a whole new path of discovery when they identified a specific pathway that played a key role in damaging the heart tissue after oxygen loss.
“We found that an acid-sensing ion channel played a significant role in causing injury to the heart. By blocking that channel, we were able to prevent some of the injury that usually occurs. So, it’s been critical to see how effective this potent, spider-derived toxin is at inhibiting the injury by blocking off this channel. All our work has shown similar promising results that we hope will eventually be seen in human trials.”
The protein has been tested in human heart cells, and the team is aiming for human clinical trials, for both stroke and heart disease, to begin within two to three years.
The Heart Foundation’s General Manager of Heart Health and Research, Bill Stavreski, welcomed the findings.
“About 57,000 Australians have a heart attack every year, and many result in permanent damage to the heart muscle, leading to heart failure, disability and reduced quality of life - while more investigation is needed, this research may lead to a new way of reversing this damage in heart attack survivors.”
This research was published in Circulation and funded by The University of Queensland, the Australian National Health and Medical Research Council, the National Heart Foundation of Australia, NSW Government, and the St Vincent’s Clinic Foundation.
The lead authors are Dr Meredith Redd (Institute for Molecular Bioscience, UQ) and Dr Sarah Scheuer (Victor Chang Cardiac Research Institute).
To learn more about new research at the Victor Chang Cardiac Research Institute view their website here.
