In a small, preliminary study, an experimental gene-editing treatment dramatically lowered cholesterol levels, perhaps permanently, after just one infusion, scientists reported on Monday.
If confirmed in larger studies, researchers hope the findings may lead to a one-and-done way to prevent heart disease in large numbers of people. Most gene therapies target rare diseases, but cardiovascular disease kills nearly 800,000 Americans a year.
“We have these debates and new guidelines that we should be treating people earlier,” said Dr. John H. P. Alexander, a cardiologist at Duke University who was not involved with the study. “A curative therapy would change the game.”
The study, published in The New England Journal of Medicine, was an interim analysis of 35 patients in a trial that will involve as many as 85 participants. All have genetically high levels of LDL cholesterol — the bad kind — or heart disease.
In the 35 patients, a single infusion of the highest dose of the treatment reduced LDL cholesterol levels by as much as 62 percent. The change has been sustained in a subgroup whose members were treated 18 months ago.
It will be followed by a larger study of 200 patients.
It is unusual for The New England Journal of Medicine to publish such a preliminary result. But “it looks like it works pretty well,” said Dr. Eric Rubin, the editor in chief. Moreover, he noted, the trial is an ambitious attempt to apply cutting-edge gene therapy to the leading cause of death in the United States.
Still, “we need much more safety data,” said Dr. J. Michael Gaziano, the director of preventive cardiology at the Boston V.A. health care system, who was not involved in the new study. The Food and Drug Administration requires that all patients in gene therapy studies be followed for 15 years.
Patients in the trial received an infusion containing a gene editing “machine,” or a tiny molecular factory wrapped in a cloak of fat. The fat-coated particles travel through the blood directly to the liver, where they are taken up by cells that remove the fatty wrapper.
The editing machine then crawls along the liver cell’s DNA until it finds its target, a gene called PCSK9. It stops there and erases one DNA letter in the gene, replacing it with another.
That simple change disables the PCSK9 gene and prevents cells from making the PCSK9 protein. Without it, the liver pulls more LDL cholesterol out of the bloodstream, keeping the levels lower.
The study was led by Dr. Sekar Kathiresan, the chief executive at Verve Therapeutics, now a subsidiary of Eli Lilly. Dr. Kathiresan, a cardiologist, said he was motivated by personal history.
His grandmother, father, uncle and brother all had heart attacks. His brother died of cardiac arrest at age 42, just after returning from a run.
Gene therapies for rare diseases carry multimillion-dollar price tags. But Dr. Daniel Skovronsky, chief scientist at Eli Lilly, said that would not be the case if this treatment were eventually approved.
“That’s not what we’re going for here,” he said. “We’re going for a medicine that someday could be part of primary care.”
High LDL levels are eminently treatable with an array of medicines, including the old standbys, daily statin pills. More recent advances include injected drugs that block the protein made by the PCSK9 gene, creating the same effect as gene editing.
But too many people cannot or will not take the drugs. Between one third and a half of patients stop taking cholesterol-lowering medications within a year of starting them, even people who have had heart attacks.
Kristy Faulkner, 45, who lives in Guilford, Conn., is among those who need treatment but are reluctant to take a powerful drug. Heart disease runs in her family, and she had a heart attack when she was 42.
“There’s some sort of internal denial, like I can’t be on these meds every day of my life,” she said.
“I understand the importance,” she added, “and I feel ashamed.”
Her cardiologist, Dr. Erica Spatz, at Yale University, is hoping Ms. Faulkner’s insurance will pay for a PCSK9 inhibitor that only has to be administered every six months. Her medical history means there is “no margin for error,” Dr. Spatz said.
But a gene-editing treatment that is administered just once?
“This kind of therapeutic breakthrough could be a game changer for people like her,” Dr. Spatz said.
Alice Thomas, 64, of Lexington, N.C., would love to take cholesterol-lowering drugs but can’t get them. Her sole source of income is Social Security, and while statins are cheap, she was unable to tolerate them.
Her insurance did not approve the injectable drugs that might have helped. She has had two strokes, and a few months ago, her LDL cholesterol level was dangerously high at 190.
“I didn’t have anything,” Ms. Thomas said. “Then I found out about this study.”
She received the infusion in Dr. Kathiresan’s trial on March 30. Two weeks later, her cholesterol level was 50.
“This is great,” she said. “One time and it’s over.”
