CRISPR Gene-Editing Therapy Shows Promising Results in Lowering Cholesterol and Triglycerides

A Phase 1 clinical trial of CTX310, an investigational CRISPR-Cas9 gene-editing therapy, demonstrated significant reductions in LDL cholesterol and triglycerides in participants with difficult-to-treat lipid disorders. The one-time intravenous infusion therapy targets the angiopoietin-like protein 3 (ANGPTL3) gene in the liver, durably turning off its expression to achieve cholesterol-lowering effects. This approach mimics natural mutations that some people are born with, providing lifelong protection against atherosclerotic cardiovascular disease without apparent harmful effects.

The trial results, presented at the American Heart Association's Scientific Sessions 2025 and simultaneously published in The New England Journal of Medicine, showed that CTX310 reduced LDL cholesterol by nearly 50% and triglycerides by about 55% on average at the highest dose. Some participants experienced reductions of up to 60% in both lipid parameters. The cholesterol-lowering effects began within two weeks after treatment and were sustained for at least 60 days of follow-up, representing the first therapy to achieve substantial simultaneous reductions in both LDL cholesterol and triglycerides.

This breakthrough has significant implications for patients with mixed lipid disorders who typically struggle with elevated levels of both cholesterol and triglycerides. According to the American Heart Association's 2025 Heart Disease and Stroke Statistics, approximately 86.4 million U.S. adults have total cholesterol levels of 200 mg/dL or higher. The Association's Lower Your LDL Cholesterol Now™ Initiative (https://www.heart.org) aims to address cholesterol management challenges through improved testing and treatment adherence.

Study author Dr. Luke J. Laffin, a preventive cardiologist at the Cleveland Clinic, described the results as unprecedented, noting that a single treatment simultaneously lowered both key lipid parameters. The therapy's potential to provide lasting effects from a one-time treatment could address one of the major challenges in cardiovascular prevention: medication adherence. Co-author Dr. Steven E. Nissen emphasized that many patients stop taking cholesterol medications within the first year, making a durable one-time treatment option particularly valuable.

The safety profile of CTX310 appeared favorable in this initial study. Three participants experienced 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 without intervention within days. 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 part of extended safety follow-up recommended by the U.S. Food and Drug Administration for all CRISPR-based therapies.

The trial involved 15 adult participants with a median age of 53 years, including individuals with various lipid disorders such as heterozygous and homozygous familial hypercholesterolemia, mixed dyslipidemia, and severe hypertriglyceridemia. All participants had elevated lipid levels despite maximum tolerated conventional therapies. The study was conducted at six sites in Australia, New Zealand and the United Kingdom between June 2024 and August 2025.

Future Phase 2 studies are planned to begin in late 2025 or early 2026, focusing on broader patient populations and long-term outcomes. These larger studies will be necessary to confirm the findings and evaluate the treatment's effectiveness across more diverse demographic groups. The current study's limitations include its small size, primarily male participant group, and geographic concentration, which may limit generalizability to other populations.

If confirmed in subsequent trials, this CRISPR-based approach could revolutionize cardiovascular prevention by eliminating the need for daily or monthly cholesterol-lowering medications for some patients with inherited lipid disorders. The durable nature of gene editing offers the potential for lifelong protection against cardiovascular disease, representing a significant advancement in precision medicine for lipid management. The full manuscript detailing co-authors, disclosures and funding sources is available in The New England Journal of Medicine (https://www.nejm.org).