US, China trials suggest a single nanodrug shot might stop bad cholesterol forever

Two recent clinical trials, one conducted in the United States and the other in China, have shown promising results for a potential "one-and-done" treatment for high cholesterol. The trials focused on using a nanodrug that employs gene-editing techniques to target and inhibit genes responsible for high levels of "bad" cholesterol, known as LDL-C, in the blood.

In the U.S. trial led by the Cleveland Clinic, researchers tested a gene-editing nanodrug called CTX310 on 15 volunteers over a period of one year. The nanodrug targets a gene called ANGPTL3, which plays a role in controlling how much fat circulates in the blood. Some individuals are born with a natural mutation that inhibits ANGPTL3, leading to extremely low cholesterol and triglyceride levels and a reduced risk of heart disease. The purpose of CTX310 is to mimic this genetic switch.

After receiving a single intravenous injection, the four volunteers who received the highest dose experienced a significant reduction in ANGPTL3 levels by an average of 78.6 percent. Their LDL-C levels dropped by 52.5 percent, and triglyceride levels fell by 47.8 percent. More importantly, the edited liver cells continued to produce new, healthy cells with the same cholesterol-lowering effect, suggesting that the treatment's impact could be permanent.

Similarly, a Chinese study published in Nature Medicine focused on patients with an inherited form of dangerously high cholesterol called familial hypercholesterolaemia (FH). People with FH have a significantly higher risk of heart attacks and typically require lifelong medication to manage their condition. The Chinese team utilized a different gene-editing tool called an adenine base editor to target the PCSK9 gene, which, when overactive, hinders the liver's ability to remove bad cholesterol from the blood.

By "switching off" PCSK9, the nanodrug allows the liver to effectively clear LDL-C from the bloodstream.

The Chinese trial likewise demonstrated promising results. In the high-dose group, LDL-C levels decreased by an average of 52.3 percent after 24 weeks, nearly double the effect seen with typical statin medications. The researchers reported that PCSK9 protein levels had dropped by 74.4 percent without any rebound increase. Participants in the Chinese study experienced only mild, temporary side effects such as fever, muscle aches, or slight liver enzyme changes.

One patient did die suddenly 179 days after receiving the lowest dose, but investigators concluded that the death was unrelated to the drug.

Both trials concluded that the gene-editing nanodrug treatments are safe. The U.S. team reported that no serious adverse events were observed during the study, while the Chinese team plans to conduct long-term follow-up research for up to 15 years to further monitor treatment effects and improve the lipid nanoparticle formulation.