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29 November 2017

New Treatment for Heart Failure — At the Start of Something Special

Regina Fritsche-Danielson
Senior Director and Head of Bioscience Heart Failure, IMED Biotech Unit, AstraZeneca

It isn’t often that a group of scientists gets to work on something as exciting as heart muscle regeneration. But a joint research team from AstraZeneca and Moderna, has seen encouraging results from stimulating new blood vessels to grow at the borders of half-dead heart muscle tissue and watching it take on a new lease of life.

Until now, our heart regeneration research has been in the laboratory. But, thanks to a highly productive collaboration between our two companies, we will soon be moving into our first Phase II clinical study in patients with heart failure who are undergoing coronary artery bypass surgery. 

Regina Fritsche-Danielson

In the area of heart failure, there is significant unmet medical need with an estimated 26 million people around the world who are living restricted lives because they have heart failure.

Heart failure occurs when the heart can’t pump blood efficiently around the body. It’s usually due to damage to heart muscle, often after a heart attack.

As heart failure occurs mainly in older people, the number affected is rising as more people live into old age. In Europe and the USA, over a million people are admitted to hospital with heart failure each year. The disease makes them breathless and fatigued, their ankles swell and they find it hard to perform daily activities that the rest of us take for granted.

Heart failure is currently treated with drugs that control blood pressure and improve the pumping action of the heart; some people benefit from a pacemaker device. But none of these gets at the underlying cause of heart failure – diseased or damaged heart muscle arising from inadequate blood supply. As a result, the outlook for people with heart failure is worse than for some types of cancer.

We’re hoping that our heart muscle regeneration research will change that. At AstraZeneca, we have an extensive cardiac regeneration research programme that is identifying new targets and pathways involved in repairing damaged heart muscle.

At the centre of our research is a naturally occurring growth factor that stimulates formation of new blood vessels and protects heart muscle cells from dying. It’s called vascular endothelial growth factor A (VEGF-A).

Researchers have known about VEGF-A for more than 30 years, and during the last 20 years tried to turn it into a treatment for heart disease. But they've had little success as they’ve been unable to control when or where it acts and for how long.

Since 2013, we’ve been working with Moderna on a different approach. We’re combining our deep understanding of vascular biology and drug formulation and development with Moderna’s well-known expertise in mRNA technology. Through this partnership, we are testing the effects of injections of VEGF-A modified mRNA in heart tissue to trigger production of VEGF-A in the precise places where we know it’s needed for improving the blood supply to damaged heart muscle.

By using the modified mRNA approach, we can deliver VEGF-A into the heart and ensure it acts locally, as well as controlling how much is made. This way we hope to reduce the risk of systemic exposure and side effects, such as leaky blood vessels and swollen tissues, which can appear if the VEGF-A signal is turned on for too long.

Perhaps the biggest breakthrough of our research came when we discovered we can inject a simple solution of ‘naked’ modified mRNA into heart muscle. This means there is no need to wrap it in a protective coating that could trigger an unwanted immune response.

This was an unexpected and exciting finding as it appears that uptake of ‘naked’ mRNA is only possible in skin and heart tissue. It enabled us to progress our research more quickly than expected.

Where do we go from here? Heart failure is our number one priority, but there are other obvious areas to take regeneration therapy, including chronic kidney disease (CKD) and serious burns and other complex wounds where there is a need to improve the blood supply to damaged tissue.

Being part of the team that is making such exciting advances is hugely rewarding. Working with Moderna, we are delighted to have already made significant progress overcoming issues and believe this is just the beginning for heart failure and other regeneration therapies.