​Media Release

Singapore clinician-scientist part of team winning £30m to end early death from killer heart diseases in global British Heart Foundation challenge

Professor Stuart Cook, from Duke-NUS Medical School and the National Heart Centre Singapore, brings to winning team CureHeart his ground-breaking research in cardiovascular medicine, which has advanced understanding of the genetic basis of cardiomyopathy and cellular processes underlying myocardial disease.

SINGAPORE, 29 July 2022 – An international team of researchers—including Professor Stuart Cook, Tanoto Foundation Professor of Cardiovascular Medicine at Duke-NUS Medical School and the National Heart Centre Singapore (NHCS)—has won £30m (approximately S$50m) to develop an injectable cure for genetic heart conditions that kill young people in the prime of their lives, as part of the British Heart Foundation (BHF)’s Big Beat Challenge. The global award is the largest in the charity’s 60-year history and presents a “once in a generation opportunity” to provide hope for families struck by these killer diseases.

The winning team, CureHeart, is composed of a global group of scientists from the UK, the US and Singapore, whose vision is to develop the first cures for inherited heart muscle diseases. To achieve this, the team will pioneer revolutionary and ultra-precise gene therapy technologies that could silence or edit the faulty genes that cause these deadly conditions. A key member of CureHeart, Prof Cook will collaborate with team members from the University of Oxford and Harvard University to explore the role of a protein, interleukin 11 (IL11), in genetic heart muscle disease using preclinical models and antibody therapies developed in Singapore.

In 2021, one in three deaths in Singapore was due to heart diseases or stroke. It is estimated that 1,000 Singaporeans die from sudden cardiac arrest every year, about half of whom are below 60 years old. Inherited heart muscle diseases can cause the heart to stop suddenly, or cause progressive heart failure in young people.

It is also estimated that one in 250 people worldwide carry faulty genes that can cause genetic heart muscle diseases, with a 50 per cent risk that they will pass them on to each of their children. In many cases, multiple members of the same family will develop heart failure, need a heart transplant, or die prematurely from sudden cardiac death at a young age. Current treatments do not prevent the condition from progressing.

The international team will take the revolutionary gene-editing technology of CRISPR to the next level by deploying ultra-precise techniques, called base and prime editing, in the heart for the first time. These ground-breaking techniques use ingenious molecules that act like tiny pencils to rewrite the single mutations that are buried within the DNA of heart cells in people with genetic cardiomyopathies.

The team has set out several approaches to achieve their mission. First, where the faulty gene produces an abnormal protein in the pumping machinery of the heart, the team will aim to correct or silence the faulty gene by re-writing the single spelling mistakes or switching off the entire copy of the faulty gene. Second, where the faulty gene does not produce enough protein for the heart muscle to work as it should, the team plan to increase the production of healthy heart muscle proteins by using genetic tools to correct the function of the faulty copy of the gene or to stimulate the normal copy of the gene. Third, they will test if treating fibrosis in patients with heart muscle disease can help improve heart function.

The team has already proven that these approaches are successful in animals with cardiomyopathies and in human cells. They believe the therapies, which could be in clinical trials within five years, could be delivered through an injection in the arm that would stop progression, and perhaps even cure, for those already living with genetic cardiomyopathies and prevent the disease developing in family members who carry a faulty gene, but have not yet developed the condition.

Prof Cook has used genetic and genomic discovery programmes in humans and human tissues, and built on these discoveries to understand disease mechanisms using functional genomic approaches in cells and model systems. His group have contributed important advances in the genetic basis of cardiomyopathy, especially the importance of titin variants around the world and troponin variants in Singaporeans, and in the cellular processes underlying myocardial disease, particularly heart fibrosis.

Prof Cook’s work in Singapore is particularly relevant as the differences in the genetic makeup of Asians from other ethnic groups are important to understand, as they impact the prevalence and course of several cardiovascular disorders. Working with his network of international collaborators, his multi-disciplinary research team works to identify new targets for diagnostic and therapeutic applications for patients who are genetically pre-disposed to cardiovascular disease.


Professor Stuart Cook, Tanoto Foundation Professor of Cardiovascular Medicine, Department of Cardiology, National Heart Centre Singapore (NHCS), and Signature Research Programme in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School: “Genetic heart muscle diseases are serious cardiovascular diseases, responsible in cardiac arrest in young people. I am honoured to play a part in this opportunity to help put an end to the suffering caused these conditions. I am especially proud of the research discoveries made by my team in Singapore at Duke-NUS and NHCS, which have helped lay some of the ground work underpinning CureHeart’s mission.”

BHF Professor Hugh Watkins, Radcliffe Department of Medicine, University of Oxford, and lead investigator of CureHeart: “This is our once-in-generation opportunity to relieve families of the constant worry of sudden death, heart failure and potential need for a heart transplant. After 30 years of research, we have discovered many of the genes and specific genetic faults responsible for different cardiomyopathies, and how they work. We believe that we will have a gene therapy ready to start testing in clinical trials in the next five years.

“The £30 million from the BHF’s Big Beat Challenge will give us the platform to turbo-charge our progress in finding a cure so the next generation of children diagnosed with genetic cardiomyopathies can live long, happy and productive lives.”

Dr Christine Seidman at Harvard University and co-lead of CureHeart: “Acting on our mission will be a truly global effort. We’ve brought in pioneers in new, ultra-precise gene editing, and experts with the techniques to ensure we get our genetic tools straight into the heart safely. It’s because of our world-leading team from three different continents that our initial dream should become reality.”

Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation: “This is a defining moment for the BHF and cardiovascular medicine. Not only could CureHeart be the creators of the first cure for inherited heart muscle diseases by tackling killer genes that run through family trees, it could also usher in a new era of precision cardiology. 

“Once successful, the same gene editing innovations could be used to treat a whole range of common heart conditions where genetic faults play a major role. The potential impact is undoubtedly transformational and will offer hope to the hundreds of thousands of families worldwide affected by these faulty genes.”

Sir Patrick Vallance, Chief Scientific Advisor to the UK Government, and Chair of the BHF’s International Advisory Panel, which selected the winning team: “CureHeart was selected in recognition of the boldness of its ambition, the scale of its potential benefit for patients with genetic heart muscle diseases and their families, and the excellence of the international team of participating researchers.”