A one-time gene-editing treatment to lower cholesterol had long-lasting effects a year later, scientists reported on Friday. The results highlight the potential to treat even common diseases by altering people’s genes.
In the small study, which followed only 15 patients, participants who got the highest dose saw their cholesterol levels plunge by half — and stay that way for a year. The results were presented at the European Society of Cardiology Congress and published in the New England Journal of Medicine.
Earlier this year, a similar “one-and-done” clinical trial that used a different gene-editing approach also reported significantly reduced “bad” LDL cholesterol in 35 patients.
Both efforts are early safety studies and are years away from becoming an option people will be offered in a doctor’s office. But an approach that once seemed almost outlandishly far out has inched closer to reality as evidence accrues that it works, and that the results stick.
“As a preventive cardiologist, you’re really thinking, I’ll treat people chronically for many, many years,” said Dr. Luke Laffin, a cardiologist at the Cleveland Clinic who led the new study. “To have the possibility of giving a one-time cure is much more akin to other specialties, like a surgeon.”
A one-and-done treatment is appealing to many patients and physicians. Despite an ever-growing armory of pills, injections and lifestyle interventions to lower the risk of heart disease, it remains the No. 1 killer of Americans. About half of people who start taking a daily statin stop, and many who could benefit from the drugs don’t start them. Lack of access to health care, an inability to tolerate the drugs and concerns about taking a medicine for life all can play a role.
In the new study, funded by the biotechnology company CRISPR Therapeutics, 15 patients received a one-time infusion of lipid nanoparticles, essentially fat bubbles, carrying gene-editing machinery to their livers. That machinery was programmed to snip and disable a gene involved in cholesterol metabolism called ANGPTL3.
The experiment was inspired, in part, by the discovery that there are people who have naturally occurring versions of the ANGPTL3 gene that aren’t functional. Those people have very low levels of cholesterol and triglycerides and a lower risk of cardiovascular disease. Gene-editing technology allows scientists to try to emulate this trait.
In the four patients who received the highest dose of the treatment, levels of LDL cholesterol and triglycerides, both risk factors for heart disease, dropped by about 50 percent and remained steady a year later.
“You do a one-time treatment; you’re done,” said Dr. Amrut Ambardekar, a cardiologist at the University of Colorado, who was not involved in the study. “You don’t have to worry about it. I think that’s what’s exciting. I think the thing that we still are trying to figure out is safety, and so far the studies have been very small.”
Dr. Kiran Musunuru, a cardiologist at the University of Pennsylvania who was not involved in the study, said, “The data look good in terms of stability.” Dr. Musunuru co-founded Verve Therapeutics, a biotech company focused on developing gene-editing for heart disease that was acquired by Eli Lilly.
CRISPR Therapeutics’ chief executive, Samarth Kulkarni, said that the results of the next phase of the trial — in a few dozen patients — were expected by year’s end. Then, discussions will begin with regulators about a large Phase 3 trial designed to test safety and efficacy. Because gene-editing is a new technology with many unknowns about safety and durability, patients are required by regulators to be followed for 15 years.
Dr. Musunuru recalled that initially, there was skepticism from companies that were more interested in using the technology on rare diseases, instead of a common killer that already has many traditional treatment options.
“I tried very hard to convince people you should work on cardiovascular disease,” he said.
Even as a proponent of the approach, Dr. Musunuru cautions that these are still the early days and that much larger studies need to be done. He predicted that this might become an option for patients in the early 2030s.
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