In a first, scientists have found evidence that gene editing could play a ‘revolutionary’ role in the treatment of high cholesterol. The experimental drug has the potential to permanently lower cholesterol.
If this becomes successful, it can provide respite to millions of high-cholesterol patients who struggle with daily lipid-lowering pills. The novel drug developed by Boston-based Verve Therapeutics, a clinical-stage genetic medicines company, uses a gene-editing method called base editing. The findings of the drug were presented on Sunday at an annual meeting of the American Heart Association.
According to a press statement by the American Heart Association, the single infusion of a CRISPR-based gene-editing therapy significantly reduced bad cholesterol in people who carry one gene for the inherited condition that results in very high LDL cholesterol levels and a high risk of heart attack at an early age.
The novel treatment involves an IV infusion of a drug that targets the PCSK9 gene which is responsible for producing bad cholesterol. The company’s preliminary study which had 10 participants revealed that 3 volunteers who were given higher doses reported a reduction in bad cholesterol levels by half.
It is noteworthy that the study was limited to people with a genetic condition called heterozygous familial hypercholesterolemia, in which cholesterol levels are sky-high from birth.
“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,” said senior study author Andrew M. Bellinger, M.D., Ph.D., chief scientific officer at Verve Therapeutics in Boston.
The ongoing, first-in-human study included 7 men and 2 women in New Zealand or the United Kingdom: average age of 54 years; 8 white adults; and 1 Asian adult.
“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.
What are the upcoming plans?
According to the company’s press statement, with the recent clearance of the IND application by the FDA for VERVE-101, Verve plans to activate and open U.S. sites.
“In 2024, the company plans to select a single dose from the dose escalation phase, initiate an expansion cohort, and complete this expansion cohort of the heart-1 clinical trial. In the first half of 2024, the company plans to initiate a phase 1 clinical trial of VERVE-102, subject to regulatory clearance,” it stated.
The company reveals that VERVE-102 is an in vivo base editing medicine that aims to inactivate the PCSK9 gene in a similar way to VERVE-101.
What are the side-effects?
A paper published in the Nature Journal reveals that The treatment came with some side effects as some participants experienced symptoms like rief flu-like symptoms, including fever, headaches and body aches, as well as a temporary increase in liver enzymes, which returned to normal within days.
However, two instances have become a cause of concern of among health experts. Two out of the ten participants experienced cardiovascular events, including one who died from a heart attack five weeks after receiving VERVE-101 and another who had a heart attack after one day.
An independent safety board concluded that the first event was expected in people who had such advanced heart disease and recommended the trial’s continuation of trial enrolment without changes.
‘Future is here’
This is the first-ever evidence that you can edit the gene of a living human and witness the clinical effect. According to experts, gene editing holds infinite opportunities as it can lead to new treatments for many genetic diseases, including cancer, heart disease, AIDS, Alzheimer’s and other ailments.
Reportedly, the Food and Drug Administration may approve the first gene-editing treatment next month for the blood disorder sickle cell disease.
