A single infusion of an experimental gene-editing treatment could prevent and treat heart disease, according to new research published in The New England Journal of Medicine.
Providence Health Care’s Mount Saint Joseph Hospital Phase 1 Clinical Trials Unit was one of a small number of sites worldwide that helped test the treatment. Early results suggest the therapy can significantly reduce “bad” cholesterol levels after a single infusion, with effects that may last for years.
The study highlights Providence’s role in advancing early-stage research that could shape future care for people at risk of heart disease.
The international trial was led by scientists from Verve Therapeutics, a wholly owned subsidiary of Eli Lilly and Company. At Providence, the research was led by Dr. Liam Brunham, an investigator with the Centre for Heart Lung Innovation, Professor of Medicine, and Canada Research Chair at the University of British Columbia. The study has drawn international attention, including coverage in The New York Times, for its potential as a “one-and-done” approach to preventing and treating heart disease.
Reimagining how cholesterol is treated
Lowering cholesterol is essential for preventing and managing cardiovascular disease. Statins are effective for many patients, but some people require additional cholesterol lowering or are unable to tolerate statins because of side effects. Newer PCSK9 inhibitors, which impact a protein in the body involved in cholesterol uptake in the liver, are very effective and have virtually no side effects, but cost thousands of dollars a year.
Both types of medications require consistent lifelong use, which can be difficult for patients to maintain. Between one-third and one-half of patients stop taking cholesterol-lowering medications within a year.
“We know that it’s often hard for patients to continue to adhere to medications in the long term,” says Dr. Brunham. “And with these types of costly medications, it also poses a real burden. This is especially true for patients with early onset heart disease, who may need to take these medications for several decades.”
A single infusion using gene editing
The therapy that this trial is investigating, known as VERVE-102, is taking a new approach. Instead of requiring ongoing treatment, it aims to use gene-editing technology to permanently deactivate the PCSK9 gene. This would enable the body to remove more LDL cholesterol, the type associated with an increased risk of heart attack and stroke, from the bloodstream.
“This is taking a very new approach to treating chronic conditions like heart disease or high cholesterol. That is to say, can we use some of these advances in gene editing to actually have a one-time treatment?” says Dr. Brunham. A one-time treatment could improve access and adherence, particularly in regions where ongoing medication availability is a barrier.
Unlike current PCSK9 inhibitor medications, which requires an injection every two weeks to six months, this therapy uses a CRISPR-based gene editing system delivered to the liver via lipid nanoparticles – a technology similar to that used in mRNA COVID-19 vaccines.
Once inside liver cells, the editing machinery makes a precise change to the DNA sequence of the PCSK9 gene, effectively shutting it off. This prevents the production of a protein that limits the liver’s ability to clear LDL cholesterol. Early data shows that this results in lower cholesterol levels in the bloodstream.
Promising early results
This Phase 1 trial included 35 participants with inherited high cholesterol or early heart disease. Each received a single intravenous infusion of VERVE-102 at varying doses. Patients within the Providence site of the trial received the treatment at the Mount Saint Joseph Phase 1 Clinical Trials Unit and were monitored closely for several days following the infusion.
Phase 1 clinical trials, where a new treatment is tested for the first time in humans, are primarily focused on determining safety and how a treatment interacts in the body. The trial found that the treatment was generally well tolerated. No dose-limiting toxic effects were reported, though some patients experienced mild infusion-related reactions such as rash or itchiness, which quickly resolved.
Researchers observed significant reductions in LDL cholesterol of up to about 62% at the highest dose, comparable to the reductions seen with biweekly PCSK9 inhibitor injections. Importantly, those reductions appeared to be sustained over time, with follow-up data showing continued cholesterol lowering for at least a year in some participants.
“That was really exciting, because it tells us that, number one, this appears to be safe, and number two, you can get the same type of benefit as you would get with an injection every two weeks with this new approach, where it could just be a one-and-done way to treat high cholesterol,” says Brunham.
A potential new era in heart disease treatment
While these initial results are promising, research on this treatment is still in early stages. The Phase 1 trial is ongoing, with additional participants being enrolled and longer-term data being collected. Future studies will involve larger patient populations to further evaluate safety and effectiveness. Regulators are also expected to require extended follow-up – potentially up to 15 years – to monitor the long-term effects of gene editing.
However, if this treatment continues to prove to be safe and effective in future studies, it could transform cholesterol management and signal a broader shift toward one-time genetic treatments for chronic diseases.
“I see this as really the beginning of what could be a totally new era in medicine, and really a completely different paradigm, where in the future we could envision shifting from the daily medication or biweekly injection model, to these one-and-done treatments,” says Brunham.
As one of a small number of sites participating in the study globally, Providence’s involvement reflects its longstanding leadership in cholesterol research and its growing role in early clinical trials. For Dr. Brunham, participation in the study was an opportunity to contribute to research at the forefront of cardiovascular medicine.
“The Verve team are really at the cutting edge of genome-editing technology,” says Dr. Brunham, “and being invited to participate in this trial was a real honour for us.”
Dr. Brunham emphasizes the Mount Saint Joseph Hospital Clinical Trials Unit team for making Providence’s participation possible.
“It’s really because of them that this was possible,” says Dr. Brunham. “I think the work that’s being done to support the development of the Clinical Trials Unit at PHC and allowing us to be a destination for these early phase clinical trials is so important, because that’s what really allows us as investigators to get to participate in these types of early-stage clinical trials, where we’re really pushing the boundaries of what’s possible in science and medicine.”
Story by Grace Jenkins, Providence Research
