Gene editing may shut off bad cholesterol

A Phase 1 clinical trial at Cleveland Clinic has shown that a single infusion of gene-editing therapy can significantly and permanently reduce cholesterol and triglyceride levels in patients whose conditions don't respond to standard medications. The trial results, presented Saturday November 8, 2025 at the American Heart Association's Scientific Sessions 2025 and published simultaneously in the New England Journal of Medicine, showed the experimental CRISPR-Cas9 treatment reduced LDL cholesterol by approximately 50% and triglycerides by about 55% in study participants. "This treatment is still very early in development but if future trials continue to demonstrate safety and efficacy, the therapy has the potential to change the way we treat lipid disorders," said Cleveland Clinic cardiologist Dr. Luke Laffin, first author of the study. "Rather than a once-daily pill or monthly injection, this therapy would potentially offer a one-time infusion that is safe and durable for patients with high cholesterol." The 15-patient trial, conducted between June 2024 and August 2025 at six sites in Australia, New Zealand and the United Kingdom, included adults ages 31 to 68 with uncontrolled high triglycerides and elevated LDL cholesterol levels. Dr. Steven Nissen, Chief Academic Officer of the Heart, Vascular & Thoracic Institute at Cleveland Clinic and senior author of the study, emphasized the revolutionary nature of the therapy. "Once the gene is edited, this is a one and done treatment," Nissen said. "This is really quite revolutionary because the alternative is to take medication every day or inject it every week or two for the rest of your life." The treatment, called CTX310, uses CRISPR-Cas9 gene-editing technology that Dr. Laffin described as "molecular scissors" that permanently switches off a gene called ANGPTL3 in the liver. People born with a naturally occurring mutation in this gene have lifelong low cholesterol and triglycerides with lower lifetime risk of heart disease and no apparent harmful effects. The trial reported no serious adverse events related to the treatment. Three participants experienced minor reactions including back pain and nausea that resolved with medication. The therapy addresses a critical adherence problem. "We know that up to 50% of people by a year after their statin prescription stop taking it," Dr. Laffin noted. Dr. Nissen explained that because high cholesterol doesn't cause symptoms, people tire of taking daily medications. For many patients, genetics determine 70-75% of their cholesterol levels. "People can eat like rabbits and exercise daily, and it's going to improve their cholesterol," Dr. Laffin explained. "But these are individuals who still can't get to the targets we need them to be to reduce their cardiovascular risk." Dr. Nissen reflected on the breakthrough: "I used to tell people, we can change everything about you, we can give you drugs, we can change your cholesterol, the only thing we can't change is your parents, cause we can't change your genes. Well, that was wrong, because now for the first time in history, we can change people's genes." Based on the positive results, Phase 2 studies are planned to begin in 2026. The researchers hope to have the therapy in Phase 3 studies within 2 to 3 years and are working to bring trials to the United States.