HEART ATTACK risk could be reduced with a single injection, according to new research. Scientists are in the process of creating the “holy grail” of gene therapy to reduce the risk of the deadly condition.
Heart attacks can occur as a result of coronary heart disease. This condition develops when the arteries become narrowed, due to poor lifestyle choices such as a high fat diet and smoking, leading to less blood and oxygen entering the heart muscle. Coronary artery heart disease is the second most common cause of death in the UK with an estimated 900,000 people currently living with heart failure or damage. Heart attacks remain the leading cause of death in the U.S.
Doctors in the US have announced plans for a radical gene therapy that aims to drastically reduce the risk of heart attack, the world’s leading cause of death, with a one-off injection.
The researchers hope to trial the therapy within the next three years in people with a rare genetic disorder that makes them prone to heart attacks in their 30s and 40s. If the treatment proves safe and effective in the patients, doctors will seek approval to offer the jab to a wider population.
“The therapy will be relevant, we think, to any adult at risk of a heart attack,” said Sekar Kathiresan, a cardiologist and geneticist at Harvard Medical School who will lead the effort. “We want this not only for people who have heart attacks at a young age because of a genetic disorder, but for garden variety heart attacks as well.”
Heart disease is the No 1 killer in many countries. An estimated 18m deaths are attributed to the condition every year, the vast majority of which, about 85%, are caused by heart attacks and strokes.
People who are at risk of a heart attack are typically put on a range of medicines, such as blood thinners, cholesterol-lowering statins, and pills for high blood pressure. Most must be taken daily for the rest of the person’s life, but many drift off their medication over time.
An experimental technique to drastically reduce the risk of heart attacks has been created by scientists which involves inserting a gene into patients cells.
The process is called gene therapy and works at correcting the effects of disease-causing mutation.
This could treat heart disease rather than using drugs or having to have surgery.
A genetic material known as microRNA-199 is delivered into a damaged heart and this causes the cells to regenerate.
British Heart Foundations chairman of cardiology, Ajay Shah, said: “A treatment that helps the heart repair itself after a heart attack is the holy grail for cardiologists. This study convincingly demonstrates for the first time that this might actually be feasible and not just a pipe dream.”
This radical therapy will modify the genes in the liver which make the Low-Density Lipoprotein (LDL) referred to as the ‘bad cholesterol.’
High levels of LDL has been found to led to heart disease and heart attack.
The single injection of nanolipids (fatty spheres) is inserted into the blood stream which slips inside the cells and then releases a molecular gene editing kit.
The aim is to mimic the natural mutation that protects against heart attacks.
Published in the journal Nature, the research saw scientists deliver microRNA-199 into pigs after a myocardial infarction.
After a month there had been “almost complete recovery” of cardiac function.
With a one-off gene therapy that permanently protects against heart attacks, the researchers hope to transform not only the impact heart disease has on lives, but the costs that health services face in caring for patients. Cardiovascular disease accounts for a quarter of all deaths in England and costs the NHS £7bn a year.
“The most exciting part of this is changing from a chronic care approach to a ‘one and done’ approach,” said Kathiresan. “We really think we can turn the tide against coronary disease by moving from a chronic care model to [eradication with] a one-time treatment.”
High cholesterol is prevalent in Kathiresan’s family. His brother and an uncle both died at age of 42 from heart attacks. Kathiresan keeps his own cholesterol under control with drugs and a healthy lifestyle. Having spent the past 15 years identifying genes that raise or lower the risk of heart attack, he has resigned from Harvard and as director of the Center for Genomic Medicine at Massachusetts general hospital to run a startup called Verve Therapeutics, which will develop the new therapy. It has received $58.5m (£45m) from investors, including a venture fund run by Google’s parent company, Alphabet.
Rather than targeting the heart itself, the therapy will modify genes in the liver that are involved in making low-density lipoprotein (LDL), often referred to as “bad cholesterol”. With age, cholesterol tends to build up in arteries and ultimately cause the blockages that lead to heart attacks.
People who are at risk of a heart attack are typically put on a range of medicines, including cholesterol-lowering statins.
Research has shown that some people carry mutations that dramatically lower their natural levels of LDL, and in turn their risk of heart attack. For example, about one in 50 African Americans has only one, instead of the usual two, working copies of a gene called PCSK9. They have extremely low cholesterol as a result. “These people are healthy and remarkably resistant to heart attack,” said Kathiresan.
The therapy will inject scores of tiny, fatty spheres called nanolipids into the bloodstream which will home in on liver cells. When the nanolipids arrive, they will slip inside the cells and release a molecular gene editing kit known as Crispr-Cas9. This finds and then disables PCSK9 or a similar gene. The aim is to turn off about 30% to 40% of PCSK9 to mimic the natural mutation that protects against heart attacks.
“The problem with all gene therapies is that you cannot withdraw people from treatment,” said Sian Harding, a professor of cardiac pharmacology at Imperial College London. “We need cholesterol for some things, and if you were to reduce it by too much it would have devastating effects on the body. It’s a problem if it’s not controllable and not reversible.”
Martin Farrall, a professor of cardiovascular genetics at the University of Oxford, said: “He’s going about it the right way. First target those individuals with extremely high LDL cholesterol, and then look at those who just by bad luck have inherited a whole load of genetic factors that put them at higher than average risk of coronary disease.
“But with gene therapy there can be a small risk of inducing cancer, so you’d want a damn good reason to do it. I’m not sure everybody in the country would want to have this jab like a vaccination.”