Oregon Health & Science University has enrolled the first participant on the West Coast in a clinical trial using gene editing to reduce a form of high cholesterol known to raise the risk of heart attack and stroke.
The multicenter, open-label trial is evaluating the safety of a one-time infusion of a lipid nanoparticle using CRISPR gene editing to inhibit the function of a gene associated with cholesterol.
“It has the potential to transform the lifetime of an individual with dangerously high levels of cholesterol,” said OHSU site investigator Ahmad Masri, M.D., M.S., associate professor of medicine (cardiovascular medicine) in the OHSU School of Medicine. “The goal is to provide a one-time therapy that could be given to an individual and reduces their cholesterol burden over decades to follow.”
OHSU is the only center on the West Coast enrolling participants in the trial, and one of 17 centers in the world testing the drug known as CTX310.
The study is enrolling people 18 to 75 years of age who are unable to control the “bad” forms of cholesterol, including triglycerides and low-density lipoprotein, or LDL, through the use of existing medications like statins.
The one-time infusion of CRISPR Cas9 nanoparticles induces a mutation in a liver gene called ANGPTL3, turning off the production of a protein that normally hinders the body’s ability to clear cholesterol.
“All of us have this gene,” Masri said. “Its job is to essentially act as a brake system to slow the clearing of cholesterol, which is useful in an evolutionary standpoint to combat starvation.”
However, too much cholesterol — especially LDL — can build up in arteries to the point that it raises the risk of heart attacks and strokes. High cholesterol is a health threat affecting an estimated 86 million adults in the United States, according to the U.S. Centers for Disease Control and Prevention.
If the new gene therapy proves to be safe and effective, Masri said it could have a profound impact on human health.
“If it works safely, it could be a choice for any adult with high LDL at elevated risk for arthrosclerosis,” Masri said. “Initially, it would be most useful for patients who can’t tolerate statins or other alternative medications — or they’re on those medications and still have high cholesterol.”
The first participant enrolled at OHSU is a 54-year-old woman whose LDL level is so high she undergoes a specialized treatment known as apharesis to remove cholesterol from the blood stream every week to control her levels. Masri said the initial participants are the most acutely affected by high cholesterol and so most likely to benefit from the new gene-editing treatment.
The clinical trial is sponsored by CRISPR Therapeutics.