The Victorian Heart Hospital and Victorian Heart Institute, in collaboration with Monash University, have spearheaded a groundbreaking trial of a gene-editing therapy aimed at permanently reducing cholesterol and triglyceride levels in patients with challenging lipid disorders. This world-first trial marks a significant advancement in cardiovascular medicine.
The early-stage study tested CTX310, an investigational CRISPR-Cas9 gene-editing therapy designed to deactivate the angiopoietin-like protein 3 (ANGPTL3) gene. This gene is a crucial regulator of blood fats linked to heart disease. Conducted globally, the Phase 1 trial involved 15 patients, including three treated at the Victorian Heart Hospital, who received a single intravenous dose of CTX310.
Mechanism and Initial Results
CTX310 employs microscopic fat-based particles to deliver CRISPR editing tools directly to the liver, targeting and disabling the ANGPTL3 gene. Individuals naturally lacking this gene exhibit lifelong low levels of LDL cholesterol and triglycerides, significantly reducing their risk of developing atherosclerotic cardiovascular disease.
The trial’s outcomes were highly promising. Within two weeks of treatment, LDL cholesterol and triglyceride levels dropped sharply and remained low for at least 60 days. At the highest dose, CTX310 achieved an average reduction of 50 percent in LDL cholesterol and 55 percent in triglycerides. Overall, participants experienced nearly a 60 percent reduction in both fats.
Importantly, CTX310 is the first therapy to demonstrate substantial reductions in both LDL cholesterol and triglycerides simultaneously, offering new hope for patients with mixed lipid disorders.
Expert Insights and Implications
Professor Stephen Nicholls, Director of the Victorian Heart Hospital and Victorian Heart Institute and the study’s lead investigator, emphasized the potential breakthrough in preventive cardiology. “The best way to treat heart disease, the leading cause of death for both men and women globally, is to prevent it,” he stated. “Gene-editing technology is a new frontier of medical treatment, and it’s incredibly exciting for Victorians and Australians that we are leading such an important trial.”
One of the major challenges in cardiovascular prevention is adherence to cholesterol-lowering medication. A one-time infusion offering long-term or permanent benefits could revolutionize treatment. “The possibility of a single-course treatment with lasting effects could be a major step in how we prevent heart disease,” Professor Nicholls added. “It makes treatment easier, reduces ongoing costs, relieves pressure on the health system – all while improving a person’s quality of life.”
Safety and Future Prospects
The Phase 1 study found the treatment to be safe and well-tolerated, with only minor and short-term side effects reported. No serious safety concerns have been observed to date. Developed by CRISPR Therapeutics, CTX310 is set to progress to larger, multinational trials planned for late 2025 or early 2026. These trials will evaluate the therapy in more diverse patient groups and assess its long-term impact on cardiovascular outcomes.
The results were presented by Professor Nicholls at the American Heart Association Scientific Sessions in New Orleans and were simultaneously published in The New England Journal of Medicine. The Phase 1 trial included participants aged 18 to 75 years across six sites in Australia, New Zealand, and the United Kingdom, all of whom had elevated lipid levels despite maximum tolerated therapy. Patients will continue to be monitored for one year, with a 15-year long-term follow-up period, as required for all CRISPR-based therapies.
Professor Nicholls said that if confirmed in future phases, CTX310 could help save millions of lives worldwide. “This trial shows that gene-editing therapy for cholesterol and triglycerides is both possible and safe,” he said. “It could change how we think about treating and preventing heart disease for generations to come.”
Conclusion
The announcement of this trial comes at a time when cardiovascular diseases remain a leading cause of mortality globally. The innovative approach undertaken by Monash University and its partners could pave the way for a new era in cardiovascular treatment, potentially transforming how lipid disorders are managed worldwide. As CTX310 moves into further testing, the medical community watches with anticipation, hopeful for a future where heart disease prevention becomes more effective and accessible.
