Flicking a single switch in people’s genetic code could bring their cholesterol under control. Permanently.
In a pilot study, published in the New England Journal of Medicine, a novel gene therapy was able to reduce patients’ low-density lipoprotein (LDL) cholesterol – 'bad' cholesterol – by almost 50 per cent, as well as triglycerides by an average of 55 per cent.
If future trials continue to be successful, then the single, one-off treatment could replace the daily cocktail of drugs millions take to control their cholesterol.
LDL cholesterol and triglycerides are fats that our livers naturally produce. If they build up in our blood, however, they can cause fatty deposits. These can lead to cardiovascular disease, which is responsible for 1 in 3 deaths in the US.
“Both LDL cholesterol and triglycerides are associated with major adverse cardiovascular outcomes such as heart attack, stroke or death,” Steven Nissen, Professor of Medicine at the Cleveland Clinic Lerner School of Medicine, in the US, told BBC Science Focus.
Nissen was part of a group that hoped to reduce people’s cholesterol levels by targeting the ANGPTL3 gene, which is associated with LDL cholesterol and triglycerides.
Around 1 in 250 people have a mutation that turns this gene off. As a result, these people have low levels of both blood fats. “Importantly, they also have a low incidence of cardiovascular disease,” said Nissen.
Fortunately, who gets the benefit of this mutation isn’t solely up to the genetic lottery anymore, thanks to CRISPR, the gene-editing technology.
Using CRISPR, Nissen and his colleagues were able to tailor the therapy to switch off the ANGPTL3 gene in the liver. It was then administered, via an infusion, to 15 patients for an preliminary trial to test its safety.
Within two weeks, the treatment substantially lowered the participants’ LDL and triglyceride levels. The study confirmed they remained low 60 days later, but according to Nissen, “These changes are expected to be permanent.”
Doctors recommend keeping LDL cholesterol levels below 100mg/dL for optimal heart health. While diet and exercise can help, many people struggle to meet this goal, particularly those with a genetic predisposition to high cholesterol.
Medications can help, but none of them lower both LDL cholesterol and triglycerides simultaneously. As a result, people often have to take multiple daily medications throughout their lives to manage their cholesterol levels.
“The next phase of the trial will begin within a few months and involve more patients with elevations in LDL cholesterol or triglycerides,” said Nissen.
If these continue to be successful, then the medication could offer a long-term weapon in the quest to defeat one of the world’s biggest killers.
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