Promising gene editing therapy lowers ‘bad’ cholesterol
Patients from Barts Health NHS Trust have received a pioneering new gene editing therapy that lowers 'bad' cholesterol after a single infusion.
Heart attacks and strokes are among the biggest causes of death in the UK. Often this is driven by high levels of low-density lipoprotein (LDL) cholesterol - known as 'bad' cholesterol - and evidence shows lowering LDL cholesterol over time reduces the risk.
Over seven million people in the UK are currently taking medications to help lower their cholesterol, such as statins, but the daily pills or regular injections can be hard to keep up with.
Up to half of people stop taking their cholesterol medication within a year of starting for various reasons. Some people find it hard to keep taking a tablet every day for many years or experience side effects.
A new therapy, called VERVE-102, is a one-off infusion. It uses gene editing to switch off the gene that tells the liver to make a protein called PCSK9. This protein usually stops the body clearing LDL cholesterol circulating in the blood. People born with a naturally inactive version of the gene have very low cholesterol throughout their lives and a much lower risk of heart disease. The therapy aims to copy that natural protection from a single treatment.
One of the patients taking part in the trial is 41-year-old Daniel Cullinane, who suffers from high cholesterol and was referred to the trial by Barts Health.
“My GP was concerned about my cholesterol levels which remained high despite being on statins plus the fact that I don’t drink or smoke” the 41-year-old explained.
“I was referred to the lipid team at Barts which led me to being put on the trial.
“My cholesterol levels have now dropped, I have lost weight and I feel a lot healthier.”
Daniel, whose father passed away from heart disease at an early age, also discovered that genetics played a part in his high cholesterol levels and has meant his family have investigated whether they have the same gene.
The first results were published on Monday (May 25) in the New England Journal of Medicine and are for a Phase 1b clinical trial meaning their primary aim is to understand the safety of the drug in a small group of patients.
The trial gave medication to 35 adults with an inherited form of very high cholesterol (heterozygous familial hypercholesterolaemia) or coronary artery disease diagnosed at a younger age than usual (premature coronary artery disease) - around a third of whom were recruited from Barts Health.
At the highest dose, the therapy reduced LDL cholesterol by up to 62%. Some people were followed for up to 18 months and the effect appeared to last. There were no serious side effects linked to this highest dose. Some people had mild reactions to the infusion and small, temporary changes in a liver test.
Professor Riyaz Patel, consultant cardiologist at Barts Health NHS Trust and Professor of Cardiology at University College London, and the trial's local lead, said: "It is still early days but this is an extremely exciting milestone. These findings show the technology works, is safe and helps lower cholesterol to levels similar to medicines we currently have.
"The therapy has the potential to provide a “one and done” approach to a very common condition, which would be transformative in preventing heart attacks and strokes over the long term.”
The trial is continuing, and larger studies are planned. The findings are also being presented at the European Atherosclerosis Society Congress in Athens. The trial is sponsored by Verve Therapeutics, a company owned by Eli Lilly.
Read the full NEJM publication here.
The story was also covered by BBC News.