Scientists are to develop the world’s first cure for genetic heart conditions by rewriting DNA in a move hailed as a “defining moment” for cardiovascular medicine.
A global team of experts from the UK, US and Singapore are joining forces to design a jab in the arm for patients to save thousands of lives after being awarded a £30m grant from the British Heart Foundation.
The team will use precision genetic techniques, called base and prime editing, in the heart for the first time to design and test the first cure for inherited heart muscle diseases, with the aim of silencing faulty genes. Animal studies have already shown the techniques work.
“This is a defining moment for cardiovascular medicine,” said Prof Sir Nilesh Samani, the BHF’s medical director.
Inherited heart muscle conditions are driven by different abnormalities in the heart but can cause sudden death or progressive heart failure. About 260,000 people have the condition in the UK, which can cause sudden death at any age.
Every week in the UK, 12 people under the age of 35 die of an undiagnosed heart condition, very often caused by an inherited heart muscle disease, also known as genetic cardiomyopathy.
All those with genetic cardiomyopathies have a 50/50 risk of passing faulty genes on to each of their children and, often, several members of the same family develop heart failure, need a heart transplant, or die at a young age.
The team behind the new research was selected by an advisory panel chaired by Prof Sir Patrick Vallance, the UK government’s chief scientific adviser.
Prof Hugh Watkins, from the University of Oxford and lead investigator of the CureHeart project, said cardiomyopathies were “really common” and affected one person in every 250 around the world.
“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,” he said. “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.”
Under the new program of research, experts hope to permanently correct or silence mutant genes involved in causing these heart problems.
Christine Seidman, a professor of medicine at Harvard Medical School in the US and co-lead of the CureHeart project, said the idea was to “fix the hearts” and revert them to more normal function.
“Most of the mutations that we find in our human patients – and while there are vast numbers of them [mutations] – they all frequently will alter one single letter of the DNA code,” she said. “That has raised the possibility that we could alter that one single letter and restore the code so that it is now making a normal gene, with normal function.”
She said some “very elegant chemistry” had already advanced this field of science, adding: “Our goals are to fix the hearts, to stabilize them where they are and perhaps to revert them back to more normal function.
“We may be able to deliver these therapies in advance of disease, in individuals we know from genetic testing are at extraordinary risk of having disease development and progressing to heart failure. Never before have we been able to deliver cures, and that is what our project is about. We know we can do it and we aim to get started.”