High cholesterol is a global health concern, with a significant percentage of the population affected. The World Health Organization (WHO) reports that nearly 40% of adults worldwide have elevated total cholesterol levels. In the United States alone, approximately 86 million adults have total cholesterol levels exceeding 200 mg/dL, while 11.5% have levels above 240 mg/dL. High levels of low-density lipoprotein cholesterol (LDL-C), also known as “bad” cholesterol, increase the risk of heart disease. Conversely, high levels of high-density lipoprotein cholesterol (HDL-C) can help lower the risk of heart disease by removing cholesterol from the bloodstream. Lifestyle choices such as an unhealthy diet, lack of exercise, and smoking, as well as genetic factors like familial hypercholesterolemia, contribute to elevated LDL-C levels. Familial hypercholesterolemia is an inherited condition that leads to high LDL-C levels and an increased risk of early-onset coronary heart disease. The current treatment for familial hypercholesterolemia involves statins or injections that target the PCSK9 gene, which controls blood LDL-C levels. However, achieving desired LDL-C levels remains challenging for many patients, with less than a quarter of those diagnosed with familial hypercholesterolemia reaching their LDL-C goals within two years of diagnosis.
Exciting progress has been made in the treatment of familial hypercholesterolemia using CRISPR-based gene editing. Researchers from the United States, the United Kingdom, and New Zealand have developed a cutting-edge gene-editing technology called VERVE-101, which has shown promising results in animal studies by effectively reducing LDL-C levels in the long term. By turning off the PCSK9 gene in the liver, the researchers were able to decrease LDL-C levels. Building on these findings, a small-scale human trial involving nine participants with familial hypercholesterolemia was conducted. These participants had persistently high LDL-C levels despite maximum doses of cholesterol-lowering medications and a history of cardiovascular disease. The researchers administered a single intravenous infusion of VERVE-101, with doses tailored to each participant’s body weight. The results showed a significant reduction in both PCSK9 protein and LDL-C levels in three participants who received higher doses of the drug. Notably, LDL-C levels decreased by 39%, 48%, and 55% in these individuals. Mild and transient side effects were observed in most participants, but two individuals with advanced coronary artery disease experienced serious cardiovascular events after the infusion.
While these findings are promising, further research is needed to address safety concerns and evaluate the long-term effects of this gene-editing technology. The researchers plan to enroll more patients in higher dose cohorts and conduct larger-scale clinical trials to assess the effectiveness and safety of the treatment. It is also important to explore the applicability, scalability, and cost-effectiveness of this approach beyond the specific subset of individuals studied. If proven effective and safe in larger and more diverse populations, this gene-editing method has the potential to revolutionize the treatment of hereditary high cholesterol by providing long-lasting effects with a one-time treatment. However, ongoing evaluation of effectiveness and safety is crucial to address any potential concerns.