Crystalline forms of cholesterol (blue) in a liver cell (purple), imaged using a scanning electron microscope.Credit: Steve Gschmeissner/Science Photo Library
A CRISPR–Cas9 gene-editing therapy has halved people’s cholesterol levels in a small clinical trial — raising hopes that, with further study, gene editing could one day be harnessed to provide a one-stop treatment for a common cause of heart disease.
For the study, researchers used CRISPR to disable a gene called ANGPTL3 that helps to regulate levels of fatty molecules, including low-density lipoprotein (LDL) or ‘bad’ cholesterol and triglycerides, in the blood. Both types of molecule are linked to an increased risk of cardiovascular disease, and levels of both fell by roughly 50% in people who were treated with the highest dose of the therapy1.
CRISPR genome-editing grows up: advanced therapies head for the clinic
So far, only 15 people have received the treatment. But, if all goes well in future studies, investigators hope that gene editing might one day liberate many thousands of people from daily regimens of cholesterol-lowering medication.
“What a revolution to be able to do that,” says Luke Laffin, a specialist in preventative cardiology at the Cleveland Clinic in Ohio and a lead investigator on the trial. “Conceptually, it’s a great idea: we can move from chronic therapy to something that’s one-and-done.”
That revolution will take years: considerably more safety testing would be needed to make the concept a reality, he adds. And there are questions about how much such a treatment would cost, and whether consumers would be willing to embrace it. But the trial results — published in the New England Journal of Medicine on 8 November — are the latest to show promise in harnessing gene-editing techniques to tackle some of the most common diseases.
Decade-long dream
“The dream scenario for me is getting these gene-editing therapies broadly applied,” says Kiran Musunuru, a cardiologist at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia. “These things are coming.”
A little over a decade ago, Musunuru wondered if CRISPR–Cas9 gene editing, then a new technology, could be harnessed to prevent or treat the world’s leading killer: cardiovascular disease. He pitched the idea to a few venture capitalists. “No one was interested at all,” he says. Instead, they wanted to focus on rare genetic disorders.
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Now, Musunuru says he knows of about a dozen companies that intend to use gene editing to tackle high cholesterol. Other cardiovascular projects include treatments for a rarer condition called transthyretin amyloidosis, which can lead to heart failure. Biotechnology company CRISPR Therapeutics in Zug, Switzerland — the sponsor of the current cholesterol trial — has begun work on a gene-editing therapy to treat high blood pressure. “It’s fertile ground,” says Musunuru, who is himself a co-founder of a company that’s pursuing similar treatments.
But shifting from rare diseases to more common ones will require big safety studies that are capable of detecting unusual side effects, and CRISPR-based therapies have been used in only a few hundred people so far.
