Research is underway on a groundbreaking gene-editing treatment aimed at combating heart disease by potentially providing a one-time solution for high cholesterol levels. Initial trials have involved a small number of participants, but early results from gene-editing technologies developed by two companies suggest that disabling specific genes could significantly reduce harmful cholesterol levels in the body. This innovation raises the possibility of preventing heart attacks without the need for long-term medication.
Dr. Luke Laffin, a preventive cardiologist at the Cleveland Clinic, expressed the public’s desire for a definitive solution rather than a temporary measure. Following the publication of a promising study in the New England Journal of Medicine, he received numerous inquiries from individuals eager to join future clinical trials. Cholesterol, while essential for the body, can lead to serious health issues when levels of low-density lipoprotein (LDL) cholesterol become excessive, resulting in plaque buildup in arteries and increasing the risk of heart disease and strokes.
Heart disease remains the leading cause of death worldwide, with millions relying on cholesterol-lowering medications such as statins. While these treatments are effective for many, some individuals struggle to achieve their cholesterol goals, and adherence is often compromised due to side effects.
Understanding the Genetic Factors
Genetic factors play a significant role in cholesterol management, alongside dietary influences. The American Heart Association notes that the liver produces the cholesterol necessary for bodily functions. Some individuals inherit genes that predispose them to high cholesterol, while others possess genetic mutations that result in naturally low cholesterol levels throughout their lives.
Research led by Dr. Kiran Musunuru, now at the University of Pennsylvania, identified a mutation in the ANGPTL3 gene that can lead to markedly lower levels of LDL cholesterol and triglycerides. Similarly, findings from UT Southwestern Medical Center revealed that loss of function in the PCSK9 gene also contributes to lower LDL levels. Dr. Steven Nissen from the Cleveland Clinic remarked on the significance of these natural genetic variations, suggesting they provide insight into the potential outcomes of gene editing.
Promising Early Results from Clinical Trials
Current injectable treatments can inhibit proteins produced by the PCSK9 and ANGPTL3 genes, assisting the body in cholesterol clearance. In contrast, the new research utilizes the CRISPR gene-editing tool to deactivate these genes in individuals with high cholesterol risks. In a recent trial, 15 participants received an infusion containing the CRISPR tool, which effectively disabled the ANGPTL3 gene in their liver cells. Within two weeks, those receiving the highest dosage experienced a 50% reduction in both LDL and triglyceride levels.
Verve Therapeutics, a subsidiary of Eli Lilly, reported similar results in a small study, where their PCSK9-targeted infusion also reduced LDL cholesterol by comparable amounts. Initial trials have taken place in Australia, the United Kingdom, and other locations, with plans for U.S. study sites to open soon. Dr. Nissen indicated that further studies focusing on CRISPR Therapeutics’ approach are expected to commence this year, although specific locations have yet to be disclosed.
Both companies are exploring multiple gene targets, but experts emphasize the need for more extensive studies to evaluate the long-term effects of gene editing. Dr. Musunuru noted that some participants from an earlier Verve study have been monitored for two years, with their cholesterol levels remaining consistently low. Unlike conventional treatments, gene editing is designed to produce permanent changes in the liver cells, which could have significant implications for cholesterol management.
Despite the potential benefits, significant safety concerns remain. Dr. Joseph Wu from Stanford University, who did not participate in the studies, pointed out that the long-term safety of CRISPR-based therapies is still unknown. The particles used to deliver the gene-editing tool may provoke liver irritation or inflammation, and there is uncertainty about whether the gene editing will exclusively target the intended genes.
Current Recommendations for Heart Health
Regardless of the outcomes of gene-editing research, the American Heart Association advocates for several key lifestyle factors that can enhance heart health. Adopting a diet rich in fruits, vegetables, whole grains, and healthy fats can help manage cholesterol levels. Reducing saturated fats can lower LDL cholesterol, while regular physical activity can boost high-density lipoprotein (HDL) levels, which is considered beneficial for heart health.
Maintaining a healthy weight, quitting smoking, and ensuring adequate sleep are crucial components of a heart-healthy lifestyle. On the medical front, managing blood pressure is essential, with optimal levels being below 120 over 80. Additionally, individuals with diabetes should prioritize controlling their blood sugar to mitigate heart risks. For those with elevated LDL cholesterol, maintaining levels around 100 is generally acceptable, but individuals with existing heart conditions are advised to lower it to at least 70.
As researchers continue to explore innovative treatments for heart disease, the potential for gene editing to transform cholesterol management remains a topic of great interest and hope.
