First-in-Human CRISPR Therapy Lowers 'Bad' Cholesterol
A landmark CRISPR-based gene editing therapy has been successfully used to lower LDL cholesterol in a first-in-human trial. The results, presented at the AHA Scientific Sessions, mark a significant step in translating gene editing technology from the lab to the clinic for common conditions. This approach could offer a one-time treatment for high cholesterol, a major risk factor for heart disease.
The therapy, developed by Verve Therapeutics, is called VERVE-101. It uses a precise form of CRISPR known as base editing to make a single, permanent change in the DNA of liver cells, switching off the PCSK9 gene. This gene provides instructions for a protein that normally allows "bad" LDL cholesterol to remain in the bloodstream. In the first-in-human "heart-1" trial, patients with a genetic condition causing high cholesterol (HeFH) received a single intravenous infusion. At the highest dose, one patient saw a 55% reduction in LDL cholesterol and an 84% reduction in the PCSK9 protein, with the effects lasting for at least 180 days. This approach is inspired by people who are naturally born with a non-functional copy of the PCSK9 gene; they experience lifelong low cholesterol and a significantly lower risk of heart disease with no known adverse effects. The goal of VERVE-101 is to replicate this natural protection with a one-time treatment, eliminating the need for daily pills or frequent injections that have low long-term adherence rates. Bringing this therapy to life requires two distinct career tracks. On one side are computational biologists and bioinformaticians who work with massive datasets to design the treatment. On the other are clinical researchers and genetic counselors who work directly with the patients testing it.
