Breakthrough Gene Editing Treatment Significantly Lowers Cholesterol

A new one-dose treatment edits a gene in the liver, disabling the ANGPTL3 protein. Early results show it can significantly lower hard-to-treat cholesterol. If the benefits prove durable and the approach remains safe over time, it could reshape how millions reduce heart-disease risk – without needing a daily pill. A research team led by Luke J. Laffin, M.D. aimed the gene therapy at a liver switch that helps set how much fat circulates through the blood. At the Cleveland Clinic, clinicians delivered the first infusion, linking a genetic idea to real patient care. That practical focus mattered because a one-and-done edit would need to outperform short-term fixes while leaving little room for error. ANGPTL3 liver protein In a phase one trial, 15 adults received a single dose and researchers monitored them closely after treatment. At the top dose for four participants, LDL cholesterol, a blood fat that forms plaque, fell 48.9% and triglycerides dropped 55.2% within 60 days. Researchers linked those changes to less ANGPTL3, a liver protein that slows fat breakdown, so enzymes cleared fatty particles faster. Two participants had serious events, including one sudden death, and three reported infusion reactions, so longer follow-up matters. Targeting ANGPTL3 with gene editing Human genetics offered a clue that disabling ANGPTL3 could protect arteries, because some people carry natural mutations. When ANGPTL3 drops, it releases brakes on enzymes that strip fat from blood particles, lowering several blood fats at once. In one large analysis, carriers of damaging variants had about 34% lower odds of coronary artery disease across many backgrounds. Editing ANGPTL3 later in life aims to copy that advantage, but it cannot recreate decades of lower exposure from birth. How the edit arrives Tiny lipid nanoparticles, fat-based carriers that protect genetic instructions, helped deliver the gene editor to liver cells. Developers packaged those carriers into CTX310, a single-infusion gene editor aimed at ANGPTL3, and clinicians infused it intravenously. Inside the liver, cells read those instructions to build CRISPR-Cas9, an enzyme guided by a matching sequence, at a chosen site. Repair machinery then seals the cut, often disrupting ANGPTL3, which can reduce the protein for as long as edited cells persist. Making a permanent change Unlike pills that wear off, gene editing can last because the liver keeps copying the changed DNA as cells divide. That lasting effect comes from a loss-of-function mutation, a change that shuts a gene down, created during DNA repair. Because the body cannot easily undo that mutation, doctors must choose dose levels carefully before giving an irreversible treatment. The appeal is strong for people who struggle with adherence, but a rare mistake could linger long after symptoms fade. Safety signals to track Even with a single infusion, safety monitoring must stretch for years because the edit happens inside living cells. Clinicians watch aminotransferases, blood markers that rise when liver cells strain, to catch inflammation before it becomes an injury. “No dose-limiting toxic effects related to CTX310 occurred,” wrote Laffin after the team reviewed early safety in treated volunteers. That reassurance still leaves open worries about unintended DNA changes, so the fine print will come from longer trials, not short-term lab tests. Who could benefit first Early candidates often include people with inherited lipid disorders or severe triglycerides that stay high despite multiple medications. One approved option, evinacumab, blocks ANGPTL3 with an antibody, so the body clears LDL cholesterol and triglycerides more efficiently. A one-time editor could appeal to patients who already take a stack of drugs and still miss their targets. Clinicians will likely reserve it for high-risk cases at first, since everyday high cholesterol already has many safe options. Access and ethical pressure Any therapy meant for large populations raises questions about who can pay, who gets offered it, and who waits. In 2022, coronary heart disease caused 371,506 deaths in the United States, so demand would far exceed early supply. Because gene edits are hard to reverse, informed consent must include long-term follow-up plans and clear rules on data use. If only wealthy systems can deliver such care, the technology could widen existing gaps in heart disease outcomes. Future of ANGPTL3 and gene editing Moving beyond an early safety study will require larger trials that enroll diverse patients and track events, not just lab results. Future testing should measure whether cutting LDL cholesterol this way also lowers heart attacks and strokes over several years. Developers also need to learn how liver health, background genes, and other medicines change the size and durability of responses. “Our trial has limitations,” wrote Laffin. The team stressed that small numbers can hide rare harms or exaggerate benefits. Together, the early human data and decades of genetics suggest that disabling ANGPTL3 might lower dangerous blood fats with one treatment. Real success will depend on proving long-term safety, showing fewer cardiovascular events, and finding ways to deliver care fairly. The study is published in The New England Journal of Medicine. —– Like what you read? Subscribe to our newsletter for engaging articles, exclusive content, and the latest updates. Check us out on EarthSnap, a free app brought to you by Eric Ralls and Earth.com. —–