Gene-editing drug cuts bad cholesterol 62% in single-dose trial
▼ Summary
– An early clinical trial for VERVE-102, a single-infusion gene-editing therapy for high cholesterol, showed no serious adverse events and was deemed safe.
– The most notable side effect was a temporary, mild increase in a liver enzyme, indicating minor liver injury where the drug works.
– Participants receiving the largest dose experienced a 62 percent reduction in LDL cholesterol, to a mean of 78 mg per deciliter.
– If sustained for over 20 years, this LDL reduction could cut the risk of cardiovascular disease from plaque buildup by an estimated 50 percent.
– VERVE-102 uses mRNA packaged in nanoparticles to deliver base-editing machinery to liver cells, enabling a single DNA base change in a specific gene.
An experimental gene-editing therapy designed to lower bad cholesterol after a single infusion has shown promising early results in a Phase I clinical trial. The drug, known as VERVE-102, aims to provide long-term cardiovascular benefits with just one dose.
Researchers published interim findings from 35 patients in the New England Journal of Medicine this week. While the data is preliminary and the sample size small, VERVE-102 appeared safe, with no serious adverse events reported, even at the highest doses tested. The only notable side effect was a temporary, mild increase in a liver enzyme, suggesting minor injury to the liver where the drug operates.
The early results also hint at significant efficacy. Among participants who received the largest dose, bad cholesterol levels , specifically low-density lipoprotein (LDL) , dropped by an average of 62 percent, bringing the mean to 78 mg per deciliter. For individuals with high cholesterol, such as those enrolled in the trial, a reduction of this magnitude could lower the risk of cardiovascular disease from arterial plaque buildup by an estimated 50 percent, provided the effect is sustained for more than 20 years. Currently, the trial has follow-up data spanning up to 18 months, and so far, the LDL reductions have held steady across all subgroups, suggesting the therapy’s benefits may be durable.
VERVE-102’s mechanism relies on an mRNA-based gene-editing platform. The mRNA is encapsulated in nanoparticles designed with surface tags that facilitate uptake by liver cells, which are central to cholesterol metabolism. Once inside the cell, the mRNA instructs it to produce an adenine base-editor protein, a modified form of the CRISPR-Cas9 gene-editing machinery that nicks just one strand of DNA. A guide RNA packaged alongside directs the base editor to a specific gene, where it makes a precise single-base change. This approach aims to permanently lower LDL production from the liver, potentially reducing the need for lifelong statin therapy.
(Source: Ars Technica)
