CRISPR cholesterol therapy continues to lower LDL levels after one year

A CRISPR-based therapy continues to reduce harmful cholesterol levels in patients after a one-year follow-up in a Phase 1 clinical trial.

A one-year follow-up of the genome-editing therapy CTX310, developed by CRISPR Therapeutics, shows continued reductions in harmful cholesterol linked to heart disease. Trial results presented at the 2026 European Society of Cardiology annual meeting revealed that the one-time infusion of CTX310 lowered 'bad' LDL cholesterol and triglycerides by approximately half. The CRISPR-based therapy achieves this by switching ANGPTL3 off in liver cells, a gene involved in lipid metabolism.

'Is something like this truly a one and done? That was always the question,' said Dr Luke Laffin, study lead and preventive cardiologist at Cleveland Clinic's Heart, Vascular and Thoracic Institute in Ohio. 'This new data is essentially saying that the decreases in LDL cholesterol and triglycerides we saw at 60 days after treatment have lasted over a year,' he added: 'In people who took the highest dose, the reduction seems durable and safe.'

The initial trial included 15 patients with dangerously high cholesterol that did not respond adequately to medication such as statins. After two months, four participants on the highest dose showed a 50 percent reduction in LDL cholesterol and a 55 percent reduction in triglycerides (see BioNews 1315); the latest data revealed that the cholesterol-lowering effect of CTX310 is durable for these patients. After one year, their average triglyceride levels remained 48 percent lower and their LDL levels remained 53 percent lower. No new treatment-related safety events were reported during the one-year follow-up.

The biological basis for the therapy emerged after scientists discovered people in Italy with genetic mutations that disable the ANGPTL3 gene. These individuals had naturally low levels of LDL cholesterol and triglycerides, as well as a decreased risk of heart disease. The therapy mimics this naturally occurring mutation by using CRISPR to render ANGPTL3 ineffective in liver cells.

'If you're 20 and you have really high cholesterol, it may make a lot more sense to have a one-time treatment that doesn't require you to have to take a pill every single day or shot every two weeks for the next 60 years,' said Professor Ann Marie Navar, preventive cardiologist at UT Southwestern Medical Centre, Dallas, Texas, who was not involved in the study. 'The potential for this is just enormous.'

The next phase of the clinical trial has begun with participants in the USA and elsewhere receiving a fixed dose equivalent to the highest dose tested in Phase 1a. Additional long-term safety follow-ups are planned for the next 15 years, as recommended by the Food and Drug Administration for all genome-editing therapies.