Imagine swapping your daily cholesterol pill for a single injection that keeps “bad” cholesterol under control for a year, a decade – or even a lifetime.
Two clinical trials, one in the United States and another in China, suggest that this one-and-done approach could become a reality.
Low-density lipoprotein cholesterol (LDL-C), better known as “bad” cholesterol, is a major driver of heart disease – the leading cause of death worldwide. Triglycerides, another type of blood fat, add to the risk.
For millions of people, the standard fix is a daily statin pill.
Research led by the Cleveland Clinic in the US and carried out in Australia, New Zealand and Britain, tested a gene-editing nanodrug called CTX310 on 15 volunteers.
The therapy uses tiny particles to carry a CRISPR gene-editing tool straight into liver cells. Its target is a gene named ANGPTL3, which helps control how much fat circulates in the blood.
Some people are born with a natural mutation that inhibits ANGPTL3. They have extremely low cholesterol and triglycerides, and they rarely develop heart disease.
CTX310 is designed to mimic that genetic switch.
The results, published in The New England Journal of Medicine on August 28, were dramatic. One year after a single intravenous injection, the four volunteers who received the highest dose saw their ANGPTL3 levels fall an average 78.6 per cent, according to the paper.
Their bad cholesterol dropped by 52.5 per cent and triglycerides fell by 47.8 per cent. Even more encouraging, the edited liver cells kept producing new, healthy cells with the same cholesterol-lowering edit – suggesting that the effect might be permanent.
It follows the publication of a paper by Chinese scientists at Shanghai Jiao Tong University’s Renji Hospital in Nature Medicine in March, which focused on patients with an inherited form of dangerously high cholesterol called familial hypercholesterolaemia (FH).
People with FH are born with faulty cholesterol-clearance machinery and face a heart attack risk 10 to 20 times higher than normal, often requiring lifelong medication.
The Chinese team used a different gene-editing tool called an adenine base editor to target the PCSK9 gene which – when overactive – destroys the liver’s ability to remove bad cholesterol from the blood. By “switching off” PCSK9, the nanodrug lets the liver clean house again.
Like the US trial, the numbers were encouraging. In the high-dose group, LDL-C fell by an average of 52.3 per cent after 24 weeks – nearly double the effect of typical statins. The team reported that the PCSK9 protein levels had dropped 74.4 per cent without creeping back up.
The teams behind both trials said their research showed the treatments to be safe. In the Chinese study, participants were reported to experience mild, temporary side effects such as fever, muscle aches or slight liver enzyme changes.
In the US study, one patient died suddenly 179 days after receiving the lowest dose. Investigators concluded the death was unrelated to the drug, according to the paper.
No other serious events were reported.
Gene editing, which has aided patients battling cancer, is now being rolled out to help fight chronic diseases because many genes that helped our ancestors survive famines or malaria have become health hazards in the modern world.
During a famine, genes that could raise blood sugar and lipid levels were advantageous but in the modern era, these genes can lead to severe metabolic problems.
Similarly, while a single thalassaemia gene continues to protect against severe malaria, inheriting severe thalassaemia leads to life-threatening anaemia.
A single nanodrug jab could rewrite those genetic instructions.
Clinical trials on hyperlipidaemia in both the US and China are still under long-term continuous observation.
“The therapy is being assessed in separate cohorts of patients with specific lipid disorders,” Cleveland Clinic cardiologist and corresponding author Steven Nissen said at the end of the American paper.
The Chinese team, when interviewed in March by the Liberation Daily outlet in Shanghai, said it would conduct long-term follow-up research up to 15 years for patients in its clinical trials to monitor treatment effects, and would also seek to improve the lipid nanoparticle formulation. -- SOUTH CHINA MORNING POST
