[Why&Next] Can a One-Time Treatment End Lifelong Medication for Hyperlipidemia?

Directly editing DNA instead of taking daily medication
Long-lasting reduction in blood lipid levels
Challenging existing treatments with lasting effects

Research into treating hyperlipidemia, which typically requires lifelong medication, with a single gene-editing treatment is gaining momentum. The approach directly alters the DNA of liver cells involved in cholesterol metabolism, allowing the therapeutic effect to last for an extended period. Recent animal studies found that the suppression of gene activity lasted for three years, while an early human trial also showed a substantial drop in cholesterol levels, drawing attention to the potential of gene editing to treat chronic diseases.

According to the international journal Nature on November 10, researchers at Verve Therapeutics, a subsidiary of Eli Lilly, released results on November 6 from animal studies of a technology that edits the ANGPTL3 gene. After a single dose of the gene-editing agent was administered to primates, levels of ANGPTL3 protein in the blood fell by an average of more than 90%, and the effect lasted for three years. In a separate animal model of hyperlipidemia, levels of low-density lipoprotein (LDL) cholesterol, known as "bad cholesterol," and triglycerides fell by approximately 40% to 50% and 50% to 70%, respectively. ANGPTL3 is a gene that produces a protein affecting the breakdown of cholesterol and triglycerides in the blood.

What stands out in this study is not only the extent of the cholesterol reduction but also how long the effect lasted. Statins, widely used to treat hyperlipidemia, inhibit cholesterol synthesis, while PCSK9 inhibitors help remove LDL cholesterol from the blood. Although these treatments have been shown to reduce the risk of heart attacks and strokes, patients must continue taking medication or receive regular injections to maintain the benefits. Gene-editing therapies, by contrast, alter the DNA of liver cells themselves, suppressing the production of proteins involved in cholesterol metabolism over an extended period.

The technology that makes this possible is base editing. Unlike conventional gene scissors, which cut both strands of DNA, it changes only specific bases to block the function of a target gene. The researchers packaged the gene-editing agent in lipid nanoparticles (LNPs), tiny particles made of fats, and delivered them to the liver. Rather than repeatedly administering drugs to inhibit a protein's activity, this approach changes the process by which the protein is produced.

This approach is also showing promise in human clinical trials. VERVE-102, which Verve Therapeutics is developing, targets the PCSK9 gene, not the ANGPTL3 gene examined in the animal study. In a Phase 1 trial involving 35 adults with genetically elevated cholesterol levels or coronary artery disease at a young age, LDL cholesterol fell by an average of 62% in the highest-dose group. The reduction also appeared to persist among the 15 participants followed for at least one year.

Other companies are also pursuing lipid disorder treatments using gene-editing technology. On November 9, CRISPR Therapeutics presented Phase 1b results for CTX310, which uses gene-editing technology, at a scientific meeting of the American Heart Association (AHA). A single dose administered to 10 patients with severe hypertriglyceridemia reduced triglyceride levels by an average of 63% after 30 days.

The growth of the hyperlipidemia treatment market is also driving global pharmaceutical companies to develop gene-editing therapies. According to market research firm Fortune Business Insights, the global dyslipidemia treatment market is projected to grow from $31.8 billion (approximately KRW 42.6756 trillion) last year to $49 billion (approximately KRW 65.758 trillion) in 2034. The therapies are still in early clinical stages, so it will take time before they can replace existing drugs. However, they are attracting attention as a new treatment approach because a single dose may produce long-lasting effects.

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