Scientists rewrite DNA to cure killer

An injectable cure for inherited heart muscle diseases that can kill young people in their prime could be available within years, after an international team of researchers were announced as the winners of the Big Beat Challenge of the British Heart Foundation.

The £30million global prize is one of the largest non-commercial grants ever awarded and presents a ‘unique opportunity’ to bring hope to families affected by these killer diseases.

The winning team, CureHeart, will seek to develop the first cures for inherited heart muscle diseases by developing breakthrough, ultra-precise gene therapy technologies that could modify or silence the faulty genes that cause these deadly diseases.

The team, made up of world-renowned scientists from the UK, US and Singapore, was selected by an international advisory committee chaired by Professor Sir Patrick Vallance, the UK government’s chief scientific adviser.

Inherited diseases of the heart muscle can cause the heart to suddenly stop or cause progressive heart failure in young people. Every week in the UK, 12 people under the age of 35 die of undiagnosed heart disease1, very often caused by one of these inherited diseases of the heart muscle, also called genetic cardiomyopathies. About half of all heart transplants are needed because of cardiomyopathy, and current treatments do not prevent the disease from progressing.

It is estimated that one in 250 people worldwide – around 260,000 people in the UK – are affected by genetic cardiomyopathies, with a 50/50 risk of passing their faulty genes on to each of their children. In many cases, several members of the same family will develop heart failure, need a heart transplant, or die suddenly of cardiac causes at a young age.

Professor BHF Hugh Watkins, from the University of Oxford’s Radcliffe Department of Medicine and CureHeart Principal Investigator, said: “This is our unique opportunity to relieve families of the constant worry of sudden death, heart failure and potential needs. for a heart transplant. After 30 years of research, we have discovered many specific genes and genetic defects responsible for different cardiomyopathies, and how they work. We believe we will have a gene therapy ready to be tested in clinical trials within the next five years.

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

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

They will focus this technology on two areas. First, when the faulty gene produces an abnormal protein in the heart’s pumping machinery, the team will aim to correct or silence the faulty gene by rewriting individual misspellings or disabling the entire copy of the faulty gene.

Second, when the defective gene does not produce enough protein for the heart muscle to function as it should, the team plans to increase the production of healthy heart muscle protein by using genetic tools to correct the function of the copy. defective gene or to stimulate the normal copy of the gene.

The team has already proven that these approaches are successful in animals with cardiomyopathies and in human cells. They believe the therapies could be delivered through an injection in the arm that would halt progression and potentially cure those already living with genetic cardiomyopathies. It could also be used to prevent the development of the disease in family members who carry a defective gene but have not yet developed the disease.

Dr Christine Seidman of Harvard University and co-lead of CureHeart, said: “Acting on our mission will be a truly global effort. We have brought in pioneers of the new ultra-precise gene editing and experts with the necessary techniques to ensure that our genetic tools penetrate directly into the heart safely. It is thanks to our leading team on three different continents that our initial dream should come true.

Professor Sir Nilesh Samani, Medical Director of the British Heart Foundation, said: “This is a watershed moment for cardiovascular medicine. Not only could CureHeart be the creator of the first cure for inherited heart muscle diseases by tackling killer genes that cross family trees, but it could also usher in a new era of precision cardiology. Once successful, the same gene-editing innovations could be used to treat a range of common heart diseases in which genetic defects play a major role. It would have a transformational impact and offer hope to the thousands of families around the world affected by these devastating diseases.

Sir Patrick Vallance, Chairman of the BHF International Advisory Group and Chief Scientific Adviser to the Government, said: “CureHeart has been selected in recognition of the boldness of its ambition, the scale of its potential benefits for patients with of genetic diseases of the heart muscle and their families, and the excellence of the international team of participating researchers.

Dr Charmaine Griffiths, Chief Executive of the British Heart Foundation, said: “With public support, the aim of the Big Beat Challenge was to move beyond incremental progress and take a giant step forward in an important area of ​​patient care. heart patients. Creating the world’s first genetic cure for heart disease would undoubtedly achieve this and could prevent families from losing loved ones without warning to these cruel diseases. However, we need the continued support of our supporters to turn science like this into a reality for the millions of people around the world living with heart disease.

Patient Testimonial – Max Jarmey, 27

Max Jarmey was just 13 when his father Chris died suddenly from cardiac arrest, caused by a condition called arrhythmogenic right ventricular cardiomyopathy (ARVC, a type of genetic cardiomyopathy).

A few years later, Max was told he had CAAL (which is now known as arrhythmogenic cardiomyopathy) following a routine screening appointment. Soon after, her younger brother Tom was also diagnosed. Both had inherited the disease from their father.

Max describes himself as “sports obsessed” growing up and he competed in mountain biking at a high level until he was 18, when his diagnosis forced him to drop out.

He said: “I’m quite robust mentally, but the first six months after my diagnosis were incredibly difficult. It was awful to be told I had a disease like ARVC at the age I was told, and then to have to leave something I loved.

Now 27, Max tries to focus on what he can do rather than what his condition prevents him from doing. He was fitted with an implantable cardioverter defibrillator (ICD), which returned his heart to normal rhythm after he went into a life-threatening rhythm – protecting him from cardiac arrest – several times over the years .

Max said: “I think the only way to deal with my ARVC is to accept it and the fact that I can’t control it. If I dwelled on it every day, it would be difficult, but I often think about it.

Professor Watkins diagnosed Max and has been his cardiologist ever since. Max said: “When Hugh told me about CureHeart I knew I wanted to be involved in something so inspiring. When I think about my future, the decision to have children and their future, CureHeart could make that decision easier. My children may never have to suffer like me with this condition. It is completely life changing.

“This project gives me hope. This is what the BHF funds – hope. It’s not just about managing the symptoms. CureHeart could be the cure for genetic cardiomyopathies.

ENDS

To request interviews or for more information, please call the BHF press office on 020 7554 0164 or email [email protected]

Notes to editors

About the British Heart Foundation

Only with public donations can the BHF continue its vital research. Help us turn science fiction into reality. Through public donations, BHF funds groundbreaking research that will bring us closer than ever to a world free from the fear of heart and circulatory disease. A world where broken hearts are mended, where millions more people survive heart attacks, where the number of people dying or disabled by strokes is halved. A world where people with heart and circulatory conditions get the support they need. And a world of remedies and treatments that we cannot even imagine today. Find out more at bhf.org.uk

About the Big Beat Challenge reward process

The BHF Big Beat Challenge is a one-time £30 million (approximately €35 million, US$36 million) research funding prize that has been designed to galvanize the international research community to identify a real-world challenge, significant unmet need, or breakthrough innovation opportunity. in cardiovascular medicine. The BHF received 75 entries, featuring team members from 40 countries. A panel of patients and the public gave their views, a special panel of independent researchers and healthcare professionals reviewed the scientific rigor of the proposals, and the final decision was made by the international advisory group composed of international personalities. leaders in science, medicine and beyond.

Find out more at bhf.org.uk/bigbeatchallenge


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