Scientists must develop the world’s first cure for genetic heart disease 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 an arm jab that could save patients thousands of lives after receiving a £30 million grant from the British Heart Foundation.
The team will use precision genetics techniques, called base and prime editing, in the heart for the first time to design and test the first cure for inherited heart muscle disease, with the goal of silencing defective genes. Animal studies have already shown that the techniques work.
“This is a defining moment for cardiovascular medicine,” said Prof. Sir Nilesh Samani, medical director of the BHF.
Inherited heart muscle disease is caused by various 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 from undiagnosed heart disease, 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 to each of their children, and often several members of the same family develop heart failure, require 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 principal investigator of the CureHeart project, said cardiomyopathies were “very common” affecting one in 250 people worldwide.
“This is our unique opportunity to relieve families of the constant worries of sudden death, heart failure and the potential need for a heart transplant,” he said. “After 30 years of research, we have discovered many of the genes and specific genetic errors that are responsible for various cardiomyopathies, and how they work. We believe that in the next five years we will have a gene therapy ready to test in clinical trials.”
Under the new research program, experts hope to permanently correct or silence the mutated genes involved in causing these heart problems.
Christine Seidman, a professor of medicine at Harvard Medical School in the US and co-leader of the CureHeart project, said the idea was to “fix the hearts” and get them to function normally again.
“Most of the mutations we find in our human patients – and although there are a large number… [mutations] – they will all often change a single letter of the DNA code,” she said. “That has raised the possibility that we can change that one letter and fix the code so that it now makes a normal gene, with normal function.”
She said a “very elegant chemistry” had already developed this field of science, adding, “Our goals are to fix the hearts, stabilize them where they are, and maybe return them to a more normal function.
“Maybe we can deliver these therapies before disease, in individuals who we know are at extraordinary risk of developing disease and developing heart failure through genetic testing. Never before have we been able to deliver cures, and that’s where our project is.” We know we can do it and we strive to get started.”