A pioneering gene-editing treatment using CRISPR technology has demonstrated the potential to permanently reduce high cholesterol and triglycerides in a small clinical trial, offering a possible one-time alternative to lifelong medications for heart disease prevention.
The study, published on November 8, 2025, in the New England Journal of Medicine and presented at the American Heart Association Scientific Sessions, involved 15 patients with severe inherited hyperlipidemia. Researchers administered a single infusion of an experimental drug that employs CRISPR-Cas9 to edit the ANGPTL3 gene in the liver, which plays a key role in regulating cholesterol and triglyceride levels. This approach was tested for safety and efficacy, with participants receiving varying doses to assess the impact on their lipid profiles.
Preliminary results showed an average reduction of nearly 50% in low-density lipoprotein (LDL) cholesterol and 55% in triglycerides at the highest dose tested. This dual effect is significant because current therapies often target only one type of fat, and many patients struggle with mixed hyperlipidemia where both are elevated. The reductions were observed within weeks of treatment and could potentially last a lifetime, based on the mechanism of gene editing.
The concept behind this therapy stems from a natural mutation found in approximately 1 in 250 individuals, where the ANGPTL3 gene is inactive, leading to lifelong low cholesterol without apparent health drawbacks. By replicating this through CRISPR, the treatment aims to provide durable protection, eliminating the need for daily pills or biweekly injections that many find burdensome. This could improve adherence, as studies show that a large portion of patients discontinue their cholesterol medications over time.
Safety data from the trial indicated that side effects were minimal, primarily consisting of mild infusion site reactions. One participant died six months after receiving the lowest dose, but investigators concluded it was due to pre-existing severe cardiovascular disease and not related to the treatment. Long-term monitoring for up to 15 years is planned to ensure no adverse effects emerge, particularly since gene editing targets only the liver to minimize risks elsewhere in the body.
Experts not involved in the study, such as Dr. Eric Topol of Scripps Research, expressed excitement about the potential but cautioned that gene-editing therapies are expensive and long-term safety remains unproven. Dr. Kiran Musunuru of the University of Pennsylvania emphasized the need for larger studies to confirm that the treatment actually reduces heart attack and stroke risks, noting that the bar for safety is higher in otherwise healthy individuals.
The drug is being developed by CRISPR Therapeutics, with similar research underway by Verve Therapeutics. Researchers plan to initiate Phase 2 and Phase 3 clinical trials soon, with hopes to complete them by the end of 2026. If successful, this could address a major unmet need, as heart disease is the leading cause of death worldwide, and poor adherence to cholesterol medications contributes significantly to its prevalence.
In summary, this gene-editing breakthrough holds promise for revolutionizing the management of high cholesterol, though it requires further validation. It represents a significant advancement in preventive cardiology, potentially offering a permanent solution that could improve public health outcomes by ensuring consistent cholesterol control and reducing the global burden of heart disease.
