Studies test whether gene-editing can fix high cholesterol. For now, take your medicine

WASHINGTON– Scientists are testing a whole new way to fight heart disease: a gene-editing treatment that could offer a one-time solution to high cholesterol.

This is very early-stage research, tested so far on only a few dozen people. But gene-editing approaches developed by two companies suggest that turning off certain genes could significantly reduce artery-clogging cholesterol, raising hopes that one day it could prevent heart attacks without having to take pills.

“People want a solution, not a Band-Aid,” said Dr. Luke Laffin, a preventative cardiologist at the Cleveland Clinic. After co-authoring a promising study published in the New England Journal of Medicine, he said he was inundated with questions about how to participate in the upcoming clinical trial.

Everyone needs a certain amount of cholesterol. But too much of it, especially a “bad” cholesterol called LDL, forms plaque on artery walls and is a leading contributor to heart attacks and strokes. Cardiovascular disease is the leading cause of death in the country – and around the world.

Millions of people take cholesterol-lowering drugs such as statins, the cornerstone of treatment. But many still struggle to lower their cholesterol levels enough, and it’s difficult to stick to the medications for life, with some even stopping because of side effects.

Although your diet contributes, your liver produces the cholesterol your body needs, according to the American Heart Association, and genes play a role in how it’s managed. Some people inherit genes that trigger very high cholesterol levels. Others have naturally extremely low cholesterol levels throughout their lives and rarely develop heart disease.

Years ago, Dr. Kiran Musunuru, a cardiologist now at the University of Pennsylvania, reported that some of these lucky people carried a mutation that turned off a gene called ANGPTL3, thereby lowering their levels of LDL cholesterol and another bad fat, triglycerides.

Separately, geneticists at UT Southwestern Medical Center discovered that other people’s extremely low LDL levels were due to the loss of function of another gene called PCSK9.

“This is a natural experiment of what would happen if we actually changed the gene,” said Dr. Steven Nissen of the Cleveland Clinic, who with Laffin oversaw an ANGPTL3 study funded by the Swiss company CRISPR Therapeutics.

There are now injected medications that block proteins produced by the PCSK9 and ANGPTL3 genes in the liver, helping the body eliminate cholesterol. The new research uses CRISPR, the Nobel Prize-winning gene-editing tool, to try to turn off one of these genes in people at high risk of uncontrolled cholesterol.

In one study, 15 adults received a single infusion of tiny particles carrying the CRISPR tool to the liver, thereby turning off the ANGPTL3 gene inside that organ’s cells. Within two weeks, those who received the highest dose saw their LDL and triglyceride levels drop by half, Laffin and Nissen reported in November.

Verve Therapeutics of Boston, a subsidiary of pharmaceutical giant Eli Lilly, reported earlier that its PCSK9-targeted editing infusion reduced LDL cholesterol by a similar amount in a small study.

The two companies’ initial studies were carried out in Australia, the United Kingdom and other countries. A Lilly spokesperson said study sites in the United States were opening. Nissen said a next-stage study of CRISPR Therapeutics’ approach is expected to begin later this year, with sites yet to be announced. Each company pursues multiple genetic targets.

Although people with naturally nonfunctional ANGPTL3 or PCSK9 have no apparent negative consequences, longer studies of the gene-editing approach in many more people are needed, said Penn’s Musunuru, co-founder of Verve. He said some participants in an earlier Verve study were followed for two years, with their cholesterol levels still lowered.

Gene editing is considered permanent. If modified liver cells reproduce, their offspring contain the modified genes, and Musunuru said the modifications lasted a lifetime in the mice.

Major safety questions remain, cautioned Dr. Joseph Wu of Stanford University, who was not involved in either study. CRISPR-based therapies for any disease haven’t been used enough to know their long-term safety — and particles carrying the gene-editing tool can irritate or inflame the liver, he said. Another unknown is whether gene editing hits only the intended target.

This is why, for the moment, studies largely target people at very high risk.

Regardless of whether gene editing ultimately comes to fruition, the American Heart Association lists eight key factors for better heart health that everyone should work on right now.

Some are about lifestyle. Eat a heart-healthy diet that includes plenty of fruits and vegetables, whole grains, and healthy fats like those found in nuts. Saturated fats can raise cholesterol, while a healthier diet can lower LDL levels and increase HDL levels, the so-called good cholesterol.

Also be physically active, as exercise can increase good HDL and help lower triglycerides.

Maintain a healthy weight. If you smoke, stop. And get enough sleep.

Medically, check your blood pressure: levels below 120 over 80 are optimal. Diabetes also harms the heart, so control your blood sugar.

When it comes to cholesterol, keeping levels of this “bad” type of LDL at 100 is considered a good thing for healthy people. But once people develop high cholesterol or heart disease, guidelines recommend lowering it to at least 70, or even lower for people at very high risk.

When lifestyle changes aren’t enough, statin pills like Lipitor, Crestor, or their cheap generic equivalents block some of the liver’s production of cholesterol and are very effective in lowering LDL. There are a few other pill options for people who need extra help or can’t take statins, as well as some injectable medications.

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