A Phase 1 clinical trial of an experimental CRISPR-Cas9 gene-editing therapy has demonstrated significant reductions in both LDL cholesterol and triglycerides with a single treatment, according to research presented at the American Heart Association's Scientific Sessions 2025. The therapy, called CTX310, uses tiny fat-based particles to deliver the CRISPR editing mechanism into the liver, where it switches off the angiopoietin-like protein 3 (ANGPTL3) gene known to regulate blood fats.
In the 15-patient trial, participants receiving the highest dose experienced reductions of up to 60% in both LDL cholesterol and triglycerides, with effects appearing within two weeks and sustained through at least 60 days of follow-up. The average reduction at the highest dose was nearly 50% for LDL cholesterol and about 55% for triglycerides. This represents 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 study participants included adults with various difficult-to-treat lipid conditions, including familial hypercholesterolemia and severe hypertriglyceridemia, who had elevated lipid levels despite maximum tolerated conventional therapies. The trial was conducted at six sites in Australia, New Zealand and the United Kingdom between June 2024 and August 2025, with participants followed for safety, cholesterol levels, and how the gene therapy was processed in the body.
Safety monitoring revealed three participants experienced minor infusion-related reactions that resolved with medication, and one participant with pre-existing elevated liver enzymes had a temporary further rise that returned to normal without treatment. No long-term or serious safety concerns were observed during the study period, 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. The full peer-reviewed manuscript was simultaneously published in The New England Journal of Medicine.
The implications of these findings are substantial for cardiovascular disease prevention. High cholesterol affects approximately 86.4 million U.S. adults according to the American Heart Association's 2025 Heart Disease and Stroke Statistics, and medication adherence remains a significant challenge. The Association recently launched the Lower Your LDL Cholesterol Now™ Initiative to address these issues. If confirmed in larger trials, this one-time gene-editing approach could transform care for people with lifelong lipid disorders and potentially eliminate the need for daily cholesterol-lowering medications.
Future Phase 2 studies are planned to begin in late 2025 or early 2026, focusing on broader patient populations and long-term outcomes. Researchers caution that as an early safety and efficacy trial with a small, primarily male group of participants from specific countries, the results may not be immediately applicable to other populations, and larger studies with more diverse participants will be needed to confirm these findings.
