Can one treatment lower cholesterol and reduce heart attack risk for years?

An experimental one-time gene editing therapy significantly lowered LDL cholesterol in an early-stage trial, raising hopes for long-term heart disease prevention after a single infusion

A one-time gene editing treatment designed to permanently lower bad cholesterol has shown encouraging early results in people at high risk of heart disease, raising hopes for a new approach to cardiovascular prevention.

 

The study, titled In Vivo Base Editing of PCSK9 with VERVE-102 for Hypercholesterolemia, published in the New England Journal of Medicine on Monday, found that a single infusion of the experimental gene editing therapy VERVE-102 significantly reduced LDL or “bad” cholesterol levels in adults with inherited high cholesterol or early coronary artery disease.

What is VERVE-102 and how does it work?

VERVE-102 is an experimental gene editing therapy developed by Verve Therapeutics, a wholly owned subsidiary of Eli Lilly and Company.

 

 

The therapy uses a technique called base editing, a newer form of gene editing that changes a single “letter” in DNA without cutting the DNA strand completely.

 

It targets the PCSK9 gene in liver cells, which regulates LDL cholesterol levels in the blood. People born with naturally inactive versions of this gene tend to have lifelong low cholesterol and a lower risk of heart attacks.

 

Researchers are trying to mimic that naturally protective effect through a one-time treatment.

 

The therapy delivers genetic instructions into liver cells to permanently switch off the PCSK9 gene. These instructions are delivered using lipid nanoparticles.

Why is the PCSK9 gene important?

According to a statement from Lilly, scientists first identified the importance of PCSK9 two decades ago when they discovered that some people naturally carried loss-of-function variants in the gene.

 

These individuals had very low LDL cholesterol levels throughout life and significantly lower rates of cardiovascular disease.

 

That discovery later led to the development of PCSK9 inhibitor drugs, which are now widely used to lower cholesterol. However, those medicines require repeated injections over time.

 

Researchers behind VERVE-102 are now exploring whether a permanent gene edit could provide long-term cholesterol lowering after a single treatment.

 

Sekar Kathiresan, senior vice-president and head of obesity research at Eli Lilly and Company and co-founder of Verve Therapeutics, said the idea emerged from studying people naturally protected from heart attacks.

 

“Nature is already running experiments for us,” Kathiresan said in a company statement.

 

He said researchers had long wondered whether the same protection could be offered to others through medicine. 

What did the study find?

The Phase 1 trial included 35 adults with heterozygous familial hypercholesterolemia, an inherited condition that causes very high cholesterol, or premature coronary artery disease.

 

Participants received a single infusion of VERVE-102 at doses ranging from 0.3 mg to 1.0 mg per kilogram of body weight.

 

The trial showed dose-dependent reductions in both PCSK9 protein levels and LDL cholesterol levels.

 

At the highest dose:

• PCSK9 levels fell by 88 per cent
• LDL cholesterol levels fell by 62 per cent
• Absolute LDL reduction reached 78 mg per decilitre

The study authors said the reductions remained stable during follow-up, which extended to at least one year in some participants.

 

According to the study, there were no reports of dose-limiting toxic effects. Some participants experienced mild-to-moderate infusion-related reactions and temporary increases in liver enzyme levels. One participant developed aspiration pneumonitis linked to pre-existing gastroesophageal reflux disease.

 

Researchers said more studies with larger groups and longer follow-up will be needed to better understand long-term safety and effectiveness.

 

Kathiresan also cautioned that the findings are still early.

 

“These are results in 35 people, and we have a lot left to learn,” he said.

 

Nearly 20 years ago, researchers discovered something fascinating: some people are naturally protected from heart attacks because one of their PCSK9 genes is turned off, leading to low cholesterol from birth.  That observation sparked a simple but ambitious question: can we give… pic.twitter.com/ezXhK1Rf08

— Sek Kathiresan MD (@skathire) May 25, 2026

 

What is familial hypercholesterolemia?

Familial hypercholesterolemia is a genetic disorder that causes very high LDL cholesterol levels from birth. According to the company statement, heterozygous familial hypercholesterolemia affects roughly one in 250 people globally.

 

The condition significantly increases the risk of early heart disease and heart attacks. Many patients need lifelong cholesterol-lowering medicines, including statins and injectable therapies, to control LDL levels.

New hope for heart care

Researchers believe gene editing therapies like VERVE-102 could eventually shift cardiovascular care from lifelong disease management to one-time prevention strategies.

 

The idea is especially important because many patients struggle with long-term adherence to cholesterol medicines over decades.

 

If future trials confirm safety and effectiveness, gene editing could potentially offer durable LDL reduction with a single infusion.

 

Kathiresan said the long-term ambition is broader than cholesterol lowering alone.

 

“I see a future free of heart attack,” he said.