A Phase 1 clinical trial of an experimental CRISPR-Cas9 gene-editing therapy safely reduced LDL cholesterol by nearly 50% and triglycerides by about 55% in participants with difficult-to-treat lipid disorders. The treatment, called CTX310, represents a potential breakthrough for patients who struggle with medication adherence and could transform cardiovascular disease prevention if confirmed in larger studies.
In the 15-patient trial conducted at six sites in Australia, New Zealand and the United Kingdom, participants received a single intravenous infusion of CTX310 at doses ranging from 0.1 to 0.8 mg/kg. The therapy uses lipid nanoparticles to deliver CRISPR editing components to the liver, where it permanently switches off the angiopoietin-like protein 3 (ANGPTL3) gene. This approach mimics natural mutations found in people who have lifelong low cholesterol and triglyceride levels without apparent harmful effects and reduced cardiovascular risk.
Results showed cholesterol and triglyceride levels began dropping within two weeks after treatment and remained reduced for at least 60 days of follow-up. At the highest dose, reductions reached up to 60% for both LDL cholesterol and triglycerides. This marks the first therapy to achieve substantial simultaneous reductions in both cholesterol and triglycerides, which is particularly significant for patients with mixed lipid disorders who often have elevations in both.
The safety profile appeared favorable, with three participants experiencing minor infusion-related reactions such as back pain and nausea that resolved with medication. One participant with pre-existing elevated liver enzymes had a temporary further increase that normalized within days without treatment. No serious safety concerns were observed, though participants will be monitored for one year within the trial and for 15 years as recommended by the U.S. Food and Drug Administration for all CRISPR-based therapies.
This development matters because high cholesterol affects approximately 86.4 million U.S. adults and is a major risk factor for heart disease and stroke, the leading causes of death worldwide. According to the American Heart Association's 2025 Heart Disease and Stroke Statistics, about 35% of American adults have total cholesterol levels of 200 mg/dL or higher. The Association recently launched the Lower Your LDL Cholesterol Now™ Initiative to address treatment adherence challenges.
Medication non-adherence remains a critical problem in cardiovascular prevention. Many patients stop taking cholesterol medications within the first year, undermining prevention efforts. A one-time treatment with durable effects could overcome this barrier and provide sustained protection against cardiovascular events. The therapy's mechanism builds on natural genetic variations, providing confidence in its biological plausibility and safety potential.
Study limitations include the small sample size, primarily male participants, and concentration in three countries, meaning results may not generalize to other populations. Participants had various lipid disorders, including familial hypercholesterolemia and mixed dyslipidemia. Larger Phase 2 studies planned for late 2025 or early 2026 will need to confirm these findings in more diverse populations and evaluate long-term outcomes.
The full peer-reviewed manuscript was simultaneously published in The New England Journal of Medicine, and preliminary results were presented at the American Heart Association's Scientific Sessions 2025. The findings represent an important step toward potentially transformative cardiovascular prevention strategies that could reduce the global burden of heart disease and stroke through durable genetic interventions.
