About 400,000 Australians have inherited and incurable cardiovascular disease. While some experience no symptoms, for others it can lead to sudden cardiac death or heart failure requiring a heart transplant.

Treatments include implanting devices to keep the heart in tune. But the surgery is invasive and is repeated every decade or so to change the batteries.  

A potential cure would be to replace the faulty genes in your heart. One approach is to use modified viruses to infect the damaged heart cells and replace or repair the damaged DNA. The technology has huge potential. But, to test its safety and efficacy you need to work with real human heart from patients with the genetic condition. That’s impossible to do safely and ethically, until now.

Professor Eddy Kizana and his Cardiac Gene Therapy Group at Westmead Institute for Medical Research have already developed genetically modified adeno-associated viruses (rAAV) that can carry the genetic repair kit.

Now, with the backing of the National Stem Cell Foundation of Australia and ABAL Banking, they’re using patient-derived stem cells to create personalised models of genetic heart disease in a dish. This involves using slices of pig heart, which have all the living cells removed, leaving behind a scaffold on which human heart muscle cells can grow.

“What we do is treat that cardiac slice with chemicals that remove all the cellular elements and what’s left is a meshwork of fibrous tissue, made up of collagen and other extracellular matrix proteins,” says Eddy.

“We then take fresh stem cells from patients, encourage them to grow into cardiac muscle cells, and introduce them to the heart scaffold. The cells find their way into the gaps to repopulate and create a piece of new cardiac tissue. So, the framework is the same, but the cellular components of that cardiac slice have now been changed over.”

Eddy says repopulation takes about three weeks, over which time electrical and mechanical stimulation is applied to encourage maturation of cardiac muscle cells so they approach what an adult heart might look like. Importantly, one with genetic heart disease.

“We can see what’s happening in real-time and know when the cells are repopulating because they start to contract and generate force.

“If you think about the way the heart works in the body, there's an electrical impulse which stimulates the mechanical beating of the heart. So, in the dish, we try and recreate those two physiological loading conditions, which also helps the culture survive beyond two to three days to about three weeks.

“And we can actually measure the force that’s being generated and get a readout about the integrity and maturity of the culture.”

For Eddy, there’s no question this is the most exciting phase of his research, moving gene therapy for genetic heart disease toward human application. He says: “The power of stem cell technology means we don’t have to wait for a patient to be getting a heart transplant to access their tissue.”  

Thanks to the Foundation’s Matched Funding Program grant, Eddy and his team are about six months away from being able to start testing efficacy of the virus vectors on models of genetic heart disease in a dish. The $100,000 grant is a collaboration between the Foundation and Westmead Institute for Medical Research (supported by a $50,000 donation from ABAL Banking).

Looking to the future, Eddy hopes to use the model in a very personalised way to predict which gene therapies will work for which patient and use that to inform therapeutics for patients with genetic heart disease.

“And the leap is that if we can develop this for genetic heart disease, when we know what the molecular or genetic problem is, we can try and extrapolate from that to the more common, acquired heart disease. The kind of heart failure that patients get after they’ve had a heart attack and scarred their hearts.”