Studies test whether gene-editing can fix high cholesterol. For now, take your medicine

Scientists are testing an entirely new way to fight heart disease: a gene-editing treatment that might offer a one-time fix for high cholesterol.

The research is in its early stages, with trials limited to a few dozen people so far. However, gene-editing approaches being developed by two companies are showing promising signs that switching off certain genes could dramatically lower artery-clogging cholesterol, potentially preventing heart attacks without requiring lifelong medication.

“People want a fix, not a bandage,” said Dr. Luke Laffin, a preventive cardiologist at the Cleveland Clinic who co-authored a study published in the New England Journal of Medicine. After the study’s publication, Laffin reported being inundated with inquiries about participating in upcoming clinical trials.

Cholesterol plays an essential role in the body, but excessive amounts, especially the “bad” LDL cholesterol, build plaque in artery walls and are a primary cause of heart attacks and strokes. Cardiovascular disease remains the leading cause of death both nationally and globally.

While millions rely on cholesterol-lowering medications such as statins, many struggle to achieve target levels. Others discontinue treatment due to side effects, highlighting the need for alternative approaches.

Genetics significantly influence how the body manages cholesterol. Some people inherit genes that cause very high cholesterol levels, while others have genetic mutations that naturally keep their cholesterol extremely low throughout their lives, protecting them from heart disease.

Dr. Kiran Musunuru, a cardiologist at the University of Pennsylvania, previously discovered that some individuals with naturally low cholesterol have a mutation that deactivates a gene called ANGPTL3, lowering both their LDL cholesterol and triglyceride levels. Similarly, geneticists at UT Southwestern Medical Center found that extremely low LDL in other people resulted from reduced function of another gene, PCSK9.

“It’s a natural experiment in what would happen if we actually changed the gene,” explained Dr. Steven Nissen of the Cleveland Clinic, who supervised an ANGPTL3 study funded by Swiss-based CRISPR Therapeutics.

Current injectable medications block proteins produced by the PCSK9 and ANGPTL3 genes in the liver, helping the body clear cholesterol. The new approach uses CRISPR, the Nobel Prize-winning gene-editing technology, to switch off one of these genes permanently in people with high-risk cholesterol profiles.

In one recent study, 15 adults received a single infusion of particles carrying the CRISPR tool to the liver, deactivating the ANGPTL3 gene. Within just two weeks, participants receiving the highest dose experienced approximately 50% reductions in both LDL and triglyceride levels.

Similarly, Boston-based Verve Therapeutics, a subsidiary of pharmaceutical giant Eli Lilly, reported comparable LDL cholesterol reductions with its PCSK9-targeted editing treatment in an earlier small study.

Both companies conducted their initial studies outside the United States, in countries including Australia and the United Kingdom. Eli Lilly has indicated that U.S. study sites are opening, while CRISPR Therapeutics plans to launch additional trials later this year.

The gene editing appears to be long-lasting. According to Musunuru, who co-founded Verve, some participants from earlier studies have been monitored for two years with sustained cholesterol reduction. In mice, the edited genes have remained altered throughout their lifespans.

However, significant safety questions remain. Dr. Joseph Wu of Stanford University, not involved in either study, emphasized that CRISPR-based therapies haven’t been used extensively enough to establish long-term safety profiles. The particles carrying the gene-editing tools may cause liver inflammation, and there’s uncertainty about whether the editing affects only the intended genetic targets.

These safety concerns explain why current studies focus primarily on individuals at very high cardiovascular risk.

While gene-editing research continues, the American Heart Association recommends eight key factors everyone should address for better heart health. These include lifestyle changes such as maintaining a heart-healthy diet rich in fruits, vegetables, whole grains, and healthy fats; staying physically active; maintaining a healthy weight; avoiding smoking; and getting adequate sleep.

Medical interventions include controlling blood pressure, with optimal levels below 120/80, managing diabetes, and keeping LDL cholesterol levels in check—ideally under 100 for healthy people and below 70 for those with existing heart disease or high-risk profiles.

When lifestyle modifications prove insufficient, medications like statins (Lipitor, Crestor, or generic equivalents) block some of the liver’s cholesterol production and effectively lower LDL. Additional pill options and injectable medications are available for those who need extra help or cannot tolerate statins.

As research progresses, gene-editing treatments may eventually offer a one-time solution for the millions battling high cholesterol, potentially transforming cardiovascular medicine and reducing heart disease’s global impact.