Bad cholesterol was reduced by 62% with one dose of the gene-editing drug in a small trial

The target gene is that which encodes the proprotein convertase subtilisin/kexin type 9 (PCSK9). This enzyme helps control the level of LDL in the blood. In particular, it promotes the destruction of LDL receptors on liver cells that can help remove LDL from circulation. Therefore, people with increased PCSK9 levels have fewer LDL receptors, and more LDL in their blood. Those with PCSK9 defects have lower LDL levels. This has been known for years, making PCSK9 a well-established target. Several drugs used in the past to treat high cholesterol work by hobbling PCSK9.

With VERVE-102, however, the goal is to permanently disrupt the gene that maintains PCSK9. Specifically, the guide RNA directs the adenine-base-editing protein to change one base in the PCSK9 gene so that it causes the cellular machinery to not read the stop signal, and the enzyme is not produced.

In the experiment, the first 35 patients were given different doses so the researchers could test the safety gradually. The first four participants started with the lowest dose of 0.3 mg per kilogram of body weight. After this went well, a second group of six people received 0.45 mg/kg. Then others received 0.6 mg/kg, 0.7 mg/kg, 0.8 mg/kg, and the final dose of 1 mg/kg, which was given to seven students. The first subgroup that received the lowest dose was followed for 18 months, while the subgroup that received the highest dose was followed for only three months so far.

The researchers observed a dose response in both PCSK9 treatments that was moderated by the magnitude of LDL reduction; increased dose, lower PCSK9, and lower LDL. At the lowest dose, PCSK9 levels decreased by 51 percent, while LDL decreased by 9 percent. At the highest dose, PCSK9 levels decreased by 88 percent and LDL decreased by 62 percent.