Gene Editing Trials Offer Hope for One-Time Cholesterol Fix, But Caution Urged
Scientists are exploring a groundbreaking new approach to combat heart disease: using gene-editing technology to potentially provide a one-time fix for high cholesterol. This early-stage research, involving only a few dozen participants so far, is being developed by two companies and shows promising hints that switching off specific genes could significantly reduce artery-clogging cholesterol levels. This raises hopes for preventing heart attacks without the need for lifelong medication.
"People want a fix, not a bandage," said Dr. Luke Laffin, a preventive cardiologist at the Cleveland Clinic. After co-authoring a promising study published in the New England Journal of Medicine, he reported being inundated with queries about participation in upcoming clinical trials.
The Role of Genes in Cholesterol Management
While diet influences cholesterol, the liver produces the cholesterol the body needs, and genetics play a critical role in its regulation. Some individuals inherit genes that cause very high cholesterol, while others have naturally low levels throughout their lives and rarely develop heart disease. Years ago, Dr. Kiran Musunuru, now at the University of Pennsylvania, identified that certain people possess a mutation that deactivates a gene called ANGPTL3, lowering both LDL cholesterol and triglycerides. Similarly, geneticists at UT Southwestern Medical Center found that extremely low LDL in others results from loss of function in another gene, PCSK9.
"It's a natural experiment in what would happen if we actually changed the gene," explained Dr. Steven Nissen of the Cleveland Clinic, who, along with Laffin, oversaw an ANGPTL3 study funded by Swiss-based CRISPR Therapeutics.
Early Gene-Editing Studies: Promises and Limitations
Currently, injected medications exist that block proteins produced by the PCSK9 and ANGPTL3 genes in the liver, aiding cholesterol clearance. The new research employs CRISPR, the Nobel Prize-winning gene-editing tool, to attempt to switch off one of these genes in high-risk individuals with uncontrolled cholesterol.
In one study, 15 adults received a single infusion of tiny particles carrying CRISPR to the liver, deactivating the ANGPTL3 gene within liver cells. Within two weeks, those receiving the highest dose experienced a 50% reduction in both LDL and triglyceride levels, as reported by Laffin and Nissen in November. Verve Therapeutics, a subsidiary of Eli Lilly, earlier noted that its PCSK9-targeted editing infusion similarly cut LDL cholesterol in a small study.
Initial studies by both companies were conducted in Australia, the UK, and other countries, with a Lilly spokesperson confirming that US sites are opening. Nissen indicated that a next-step study of CRISPR Therapeutics' approach should commence later this year, though locations remain unannounced. Each company is investigating multiple gene targets.
While individuals with naturally nonfunctioning ANGPTL3 or PCSK9 show no apparent adverse effects, longer-term studies involving many more participants are necessary, cautioned Penn's Musunuru, who co-founded Verve. He noted that some participants in an earlier Verve study have been tracked for two years, with cholesterol levels still lowered. Gene editing is considered permanent; if edited liver cells reproduce, their progeny retain the altered genes, and Musunuru stated that edits have lasted a lifetime in mice.
Major safety questions persist, warned Dr. Joseph Wu of Stanford University, who was not involved in either study. He highlighted that CRISPR-based therapies for any disease have not been used extensively enough to assess long-term safety, and the particles delivering the gene-editing tool can cause liver irritation or inflammation. Another uncertainty is whether gene-editing precisely hits only the intended target, which is why current studies primarily focus on very high-risk individuals.
Current Heart Health Recommendations
Regardless of gene editing's future, the American Heart Association emphasizes eight key factors for better heart health that everyone should address now:
- Lifestyle adjustments: Adopt a heart-healthy diet rich in fruits, vegetables, whole grains, and healthy fats like nuts. Reduce saturated fats to lower LDL and increase HDL, the "good" cholesterol.
- Physical activity: Regular exercise can boost HDL and help lower triglycerides.
- Weight management: Maintain a healthy weight.
- Smoking cessation: Quit smoking if applicable.
- Sleep: Ensure adequate sleep.
- Medical controls: Manage blood pressure optimally below 120/80 and control blood sugar to prevent diabetes-related heart damage.
For cholesterol, healthy individuals should aim for LDL levels around 100, but those with high cholesterol or heart disease are advised to lower it to at least 70, or even lower for high-risk cases. When lifestyle changes are insufficient, statin pills like Lipitor or Crestor, or their generic equivalents, effectively block some liver cholesterol production. Additional pill options and injected medicines are available for those needing extra help or unable to take statins.
The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute's Department of Science Education and the Robert Wood Johnson Foundation, with the AP solely responsible for all content.
