In a groundbreaking development, a novel gene-editing therapy using CRISPR technology, which employs a technique for precisely rewriting the genetic code directly in the body, has significantly reduced low-density lipoprotein cholesterol (LDL-C), or ‘bad’ cholesterol.
This reduction, potentially lasting a lifetime, was observed in three individuals prone to dangerously high cholesterol levels.
The therapy’s success is attributed to a blood infusion of a so-called base editor, specifically designed to disable the PCSK9 liver protein that plays a key role in cholesterol regulation, thereby offering a transformative approach to treating high cholesterol and heart disease.
Transformative Results from the First Human Trial
The therapy, named VERVE-101, targets the PCSK9 gene in the liver, a critical factor in regulating blood LDL-C levels. In the first human trial, presented at the American Heart Association’s Scientific Sessions 2023 in Philadelphia, the therapy demonstrated substantial LDL-C reduction in participants with heterozygous familial hypercholesterolemia – a condition that predisposes individuals to high cholesterol and early heart attacks.
A Potential Game-Changer in Cholesterol Management
Andrew M. Bellinger, M.D., Ph.D., the study’s senior author and Chief Scientific Officer at Verve Therapeutics, emphasized the potential of VERVE-101 to replace daily pills or intermittent injections with a single-course therapy that could offer decades of benefits.
He said: “Instead of daily pills or intermittent injections over decades to lower bad cholesterol, this study reveals the potential for a new treatment option – a single-course therapy that may lead to deep LDL-C lowering for decades.”
Study Details and Promising Outcomes
The ongoing trial included 9 participants from New Zealand and the United Kingdom, suffering from high LDL-C despite maximum-tolerated medication. Each participant suffered from heterozygous familial hypercholesterolemia.
The results were encouraging.
Participants administered a dose of 0.45 mg/kg experienced a significant reduction in LDL-C levels, averaging 39% and 48%. The participant who received a dose of 0.6 mg/kg saw a 55% decline in LDL-C. Additionally, these doses also led to substantial reductions in blood PCSK9 protein levels, with decreases recorded at 47%, 59%, and 84% among the three participants receiving 0.45 mg/kg or 0.6 mg/kg doses.
A six-month follow-up of the participant treated with the 0.6 mg/kg dose revealed a sustained reduction in LDL-C, highlighting the potential for long-term benefits of this therapy. Continuous monitoring of these participants is ongoing to further understand the lasting impacts of the treatment.
“We were thrilled to see that the previous testing we had done of VERVE-101 in animal models translated faithfully to these findings in humans,” Bellinger said.
The Long Road Ahead
The study highlights the need for larger, controlled trials to fully establish VERVE-101’s efficacy and safety.
“The next steps for the study are that we’re enrolling more patients in the 0.45 mg/kg and 0.6 mg/kg cohort and plan to enroll larger studies, expansion cohorts and a randomized placebo-controlled study in 2025,” Bellinger said.
“The heart-1 trial demonstrated the first human proof-of-concept for in vivo DNA base editing. We saw dose-dependent reductions in blood LDL and blood PCSK9, and those reductions were clinically meaningful.”
Impact on Familial Hypercholesterolemia
An estimated 1.3 million adults and children in the U.S. are affected by familial hypercholesterolemia. This therapy could significantly reduce the risk of heart disease in these individuals, offering a ray of hope for those grappling with this genetic condition.
VERVE-101 represents a significant leap forward in the treatment of high cholesterol and heart disease. This innovative approach, if proven safe and effective in future studies, could redefine cardiovascular care, providing long-term relief for millions at risk of heart disease.