BREAKING: Single-Infusion Gene Therapy Slashes Cholesterol Levels in Early human Trial
A novel gene therapy, CTX310, dramatically reduced “bad” cholesterol and triglyceride levels in a small, early-stage clinical trial, offering a potential one-time treatment for high cholesterol. Results published this week demonstrate that a single infusion of the therapy lead to nearly a 50% decrease in LDL cholesterol and a 55% reduction in triglycerides in some participants.
the trial, involving 15 participants from Australia, New Zealand, and the U.K., targeted the ANGPTL3 gene. This gene produces a protein that inhibits the liver’s ability to break down cholesterol. By effectively “turning off” the gene, CTX310 aims to mimic the effects seen in individuals with naturally low-functioning versions of ANGPTL3, who experience lifelong reductions in cholesterol and triglyceride levels.
At the trial’s outset, the median LDL cholesterol level among participants was 155 mg/dL, and the median triglyceride level was 192 mg/dL – both significantly above healthy thresholds (LDL below 100 mg/dL and triglycerides below 150 mg/dL). Participants, primarily in their 50s and 60s (13 men), all had uncontrolled high LDL, triglycerides, or a combination of both.
Those receiving the highest dose of CTX310 experienced a 48.9% reduction in LDL cholesterol and a 55.2% drop in triglycerides within two months of treatment.
While the treatment was generally well-tolerated,a few participants reported mild side effects like nausea or back pain during the up-to-four-hour infusion. One participant experienced a temporary increase in liver enzymes, which later normalized. One death occured, but researchers stated it was unrelated to the infusion and happened months afterward.
“What’s nice about this target of ANGPTL3 is that it not only lowers the LDL, the bad cholesterol, but it also has some effectiveness on people who have very high triglycerides,” explained Dr. Elizabeth McNally, a human geneticist and cardiologist at the Northwestern Feinberg School of Medicine in Chicago, who was not involved in the study. “This could be helpful, but it really does remain to be seen how this is better than existing therapies.”
This trial builds on growing momentum in gene therapy for cholesterol management. Two similar studies presented at the American Heart Association meeting in 2023 also explored gene-targeting approaches to lower cholesterol, with larger trials currently underway.
The growth of CRISPR technology, first utilized in 2012 and recognized with the 2020 Nobel Prize in Medicine, has paved the way for these advancements. In 2023, the FDA approved Casgevy, the first CRISPR-based drug in the U.S., for the treatment of sickle cell disease.
Researchers,led by Dr. Nissen, plan to expand clinical trials to include a larger and more diverse patient population, including participants in the U.S. “We’ve got a ways to go, but this is the door to the future,” Nissen stated.
