(CNN) — A one-time snip of a key gene lowered heart-clogging cholesterol by about 50% over an entire year with no adverse effects, scientists have reported.
The overwhelmingly positive results were found in four people who had taken the highest dose of the experimental treatment during a pilot study published in The New England Journal of Medicine in November 2025.
That study was extremely small — only 15 patients with dangerously high cholesterol that did not respond to medication. The research was designed to test the safety of five different doses of a gene-altering infusion delivered by CRISPR-Cas9, a biological scissor which cuts a targeted genetic location to modify or turn a gene on or off.
“If you’d asked me 15 years ago if we could have done something like this, I would have thought you were crazy,” senior study author Dr. Steven Nissen, chief academic officer of the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at Cleveland Clinic in Ohio, told CNN previously.
An update on the study, published Friday in NEJM, appears to answer a key question: Does the intervention last?
“Is something like this truly a one and done? That was always the question,” said lead study author Dr. Luke Laffin, a preventive cardiologist at Cleveland Clinic’s Heart, Vascular & Thoracic Institute.
“This new data is essentially saying that the decreases in LDL cholesterol and triglycerides we saw at 60 days after treatment have lasted over a year,” Laffin said. “In people who took the highest dose, the reduction seems durable and safe.”
Low-density lipoprotein, or LDL, is known as “bad” cholesterol. It plays a major role in heart disease — the No. 1 killer of adults in the United States and worldwide. Triglycerides are a different type of fat in the blood that is also linked to an increased risk of cardiovascular disease.
If larger clinical trials show similar results, the procedure could be a game changer for young people with severe disease, preventive cardiologist Dr. Ann Marie Navar, an associate professor of cardiology at UT Southwestern Medical Center in Dallas, told CNN previously.
“If you’re 20 and you have really high cholesterol, it may make a lot more sense to have a one-time treatment that doesn’t require you to have to take a pill every single day or shot every two weeks for the next 60 years,” said Navar, who was not involved in the study. “The potential for this is just enormous.”
The findings are also exciting because so many patients of all ages forget to take their daily medications to control high cholesterol levels, Navar said: “In spite of having a lot of available therapies, the majority of people do not have their LDL under control.”
Researchers estimate only half of people take their cholesterol meds more than 80% of the time, and between 33% to 50% discontinue their statin medication within a year after starting treatment.
A lucky mutation reduces risk of heart disease
The idea for a gene-editing treatment came from an unusual source — a genetic mutation in the ANGPTL3, or angiopoietin-like protein 3 gene, which is responsible for regulating LDL and triglycerides.
In people with this gene mutation — which experts say applies to about 1 in 250 people in the United States — one or both copies of ANGPTL3 is shut off. The result is dramatic, Laffin said: extremely low levels of LDL cholesterol and triglycerides for life without any apparent negative consequences. Having the mutation also drastically lowers or even eliminates a person’s risk for heart disease.
“It’s a naturally occurring mutation that’s protective against cardiovascular disease,” said Nissen, who holds the Lewis and Patricia Dickey Chair in Cardiovascular Medicine at Cleveland Clinic. “And now that CRISPR is here, we have the ability to change other people’s genes so they too can have this protection.”
In people with the natural mutation, every cell in the body has the deactivated ANGPTL3 gene. The new CRISPR-Cas9 therapy, however, focuses only on the liver — the organ responsible for synthesizing triglycerides and producing cholesterol while also removing any excess from the bloodstream.
That targeting is reassuring for the long-term safety of the drug’s impact, Nissen said, making it less likely that genes in other parts of the body could also be edited.
The highest dose worked best
In the study, one group of people received a tiny dose of 0.1 milligrams per kilogram of the CRISPR-based drug, while others received 0.3, 0.6, 0.7 and 0.8 milligrams per kilogram, Laffin said.
When measured at two months post-infusion, people who got the highest dose — 0.8 milligrams per kilogram — had an average 55% decrease in triglycerides and nearly 50% reduction in LDL cholesterol. At one year, the average triglyceride levels of these study participants were nearly 48% lower and cholesterol levels dropped by almost 53%.
Medications available today can already lower LDL cholesterol to the levels found in the study.
“In fact, some medicines are a little more potent,” Dr. Pradeep Natarajan, director of preventive cardiology at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School in Boston, told CNN previously.
A typical LDL level is around 100. However, cardiologists may prefer that people with existing heart disease, or those born with hard-to-control cholesterol, lower their LDL cholesterol levels to 40 or 50. That’s very hard to do through diet and lifestyle, said Natarajan, who was not involved in the study.
Side effects of the initial treatment were minimal, mostly irritation at infusion sites, according to the study. One person suffered a spinal disk herniation, and another had an increase in enzymes that could signal liver damage, but those levels resolved within two weeks.
However, one person died six months after the infusion. “He had extensive, advanced cardiovascular disease, and he got the tiniest 0.1 dose, a dose that doesn’t do anything,” Nissen said.
“We don’t think that his death has any implications to the study at all,” Nissen said. “In addition, the FDA has recommended these people be followed after the trials are all over for 15 years to see if there are long-term adverse effects. That will be done.”
There was also a 20% reduction in HDL or high-density lipoprotein, known as “good cholesterol,” at both two months and one year after treatment.
A new clinical trial, with up to 40 people receiving the highest dose of treatment, is underway in the US and Australia. Those findings should further refine long-term expectations, Laffin said. Research must then move to phase 2 and phase 3 clinical trials and be approved by the US Food and Drug Administration before the procedure could be more widely available — a process that can often take years.
“One of the amazing results of the study has been the public response asking if they can be involved with these clinical trials,” Laffin said. “People were calling the American Heart Association, calling us at Cleveland Clinic — there’s a lot of enthusiasm. We didn’t know patients would be willing to undergo genetic treatment, but clearly, they are.”
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