Brits at risk of heart attack should try radical drug to lower their ‘bad’ cholesterol
- Verve-101 erases an inherited defect that causes life-threatening cholesterol
- Statins reduce the level by 30 to 50 percent, but only work if taken regularly
- Volunteers from the UK will join Americans for the 40-strong study this year
- All 40 patients inherited high cholesterol and suffered a heart attack
Britons at high risk of heart attack are set to take part in a trial of a gene-editing drug that promises to permanently lower cholesterol levels.
The breakthrough drug, codenamed Verve-101, eradicates a tiny hereditary defect that causes life-threatening levels of the lipid in the blood.
A patient in New Zealand recently became the first in the world to receive an infusion. British volunteers will join others from America later this year as part of a 40-person study to test whether the treatment lowers “bad” LDL cholesterol in humans – and by how much.
Previous studies in monkeys, which share the same cholesterol gene, PCSK9, have shown remarkable success. LDL fell nearly 70 percent, with the same levels still observed two years later, suggesting the drop may be permanent.
Codenamed Verve-101, the gene-editing drug erases a tiny genetic defect that causes life-threatening levels of the lipid in the blood
Cardiologist and geneticist Dr. Sekar Kathiresan, co-founder of Verve Therapeutics, the team behind Verve-101, said, “If it works and it’s safe, this is the answer to heart attacks – this is the cure.”
Each of the 40 patients in the study will have inherited from a parent a naturally high level of cholesterol – a condition known as familial hypercholesterolaemia (FH) which affects one in every 250 Britons. Everyone will have had a heart attack at some point.
Studies show that the longer LDL is kept low, the better the chance of preventing heart attacks.
While statins are effective at lowering cholesterol — typically by 30 to 50 percent — they must be prescribed by a doctor and only work if people take them regularly.
But dr Kathiresan said a US study showed that only half of people who have had a heart attack are taking medication to lower cholesterol, leading to “additional heart attacks, strokes and even death.”
Verve-101 uses a precision gene-editing technique called CRISPR base editing to remove a single “incorrect” letter of the DNA code before replacing it with a “harmless” one. The effect is that cells in the liver, where cholesterol is made, produce far less fatty LDL, which can clog arteries.
Like Pfizer-BioNTech and Moderna’s Covid vaccines, Verve-101 uses messenger RNA (mRNA) to instruct cells.
In the case of vaccines, the mRNA tells them to mass-produce the Covid virus’s spike protein so the immune system can recognize the original when it shows up. In Verve-101, the mRNA tells the liver cells to make two proteins – one to localize the PCSK9 gene and another to edit it.
dr Kathiresan said a US study showed that only half of people who have had a heart attack take cholesterol-lowering drugs, leading to “additional heart attacks, strokes and even death.”
As with vaccines, the mRNA is wrapped in a tiny sac of fat called “lipid nanoparticles” that helps it enter cells. dr Kathiresan said he was “optimistic” that UK regulators would allow the trial to begin later this year. If everything goes well, Verve will publish the first results in 2023 and hopes that the drug will be available by 2028.
Cholesterol is produced by the liver and transported throughout the body in the blood. The body needs cholesterol to build healthy cells, but high levels can increase your risk of heart disease.
In FH, there is a defect in one of the genes involved in removing cholesterol from the blood, which can lead to a build-up.