High cholesterol is an issue on the minds of many Kiwis, but new Messenger RNA technology could soon put such anxiety to bed and help save thousands of lives each year.
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High cholesterol causes heart disease, the leading cause of premature death in New Zealand today.
For those battling with high cholesterol, many have been prescribed life-long, daily medication, which still doesn’t guarantee low-enough cholesterol levels to avoid the disease. But there is new hope with recent medical advances.
In New Zealand just a few weeks ago, a person was injected with new gene-editing material designed to modify the DNA which produces bad cholesterol – a world first in medicine.
The experiment, part of a clinical trial by the US biotechnology company Verve Therapeutics, involved injecting a version of the gene-editing tool CRISPR in order to modify a single letter of DNA in the patient’s liver cells.
The trial is being hailed as revolutionary. Dr Ralph Stuart, The Heart Group and Auckland City Hospital cardiologist, tells Jesse Mulligan it is an exciting development, potentially offering a life-long protection from high cholesterol.
Cholesterol travels through the blood on proteins called lipoproteins. Two types of lipoproteins carry cholesterol throughout the body:
Low-density lipoprotein (LDL), or “bad” cholesterol, makes up most of your body’s cholesterol. High levels of LDL raise your risk for heart disease and stroke.
High-density lipoprotein (HDL), or “good” cholesterol, absorbs cholesterol and carries it back to the liver. The liver then flushes it from the body.
When your body has too much LDL, cholesterol can build up on the walls of your blood vessels. This buildup is called “plaque.” As your blood vessels build up plaque over time, the insides of the vessels narrow. The narrowing blocks blood flow to and from the heart and other organs.
Now, with an injection, medical science may radically address the danger at a genetic level. The trial follows studies that identified why some unique people simply don’t get high cholesterol.
“The new technology targets a protein called PCSK9, which is in the liver,” Stuart says.
“This protein was actually identified from genetic studies where they were looking at families who had incredibly low cholesterol levels in the blood and didn’t get any heart disease. They were trying to identify why, and the genetic analysis identified the protein.
“Essentially what it does is destroy the cholesterol receptors, so they don’t work so well. Then HDL cholesterol goes very high in the body. So, it actually turns out if you don’t have this protein PCSK9 you’re much better off and it doesn’t seem to have any harm otherwise.
“So, these people who had this genetic abnormality worked perfectly well in every other respect and they didn’t get any heart disease and low cholesterol. So, that was the start of the journey and along the way they targeted this particular protein."
He says there are now drugs already available in New Zealand that use a monoclonal antibody to bind to the PCSK9 and stop it working properly.
“You can have an injection that knocks out the PCSK9 and knocks it down to a lower level,” he says.
The treatment is currently expensive Stuart says and works for about one month, before another injection is needed.
He says there is another one called Inclisiran, approved by the FDA, which uses a segment of our DNA to block the gene that produces PCSK9.
Last year the National Health Service in England said that, by lowering levels of bad cholesterol, inclisiran could prevent 55,000 heart attacks and strokes, with the potential to save 30,000 lives within the next 10 years.
“You inject the MRNA and it finds the PCSK9 gene and blocks it, and then you don’t produce it for that reason and your cholesterol falls. So that’s also being evaluated in New Zealand now,” Stuart says.
That injection needs to be taken between every six months and every year.
This new third treatment method takes the new technology one step further, by changing the gene itself.
“It finds and uses a little bit of MRNA to scout the DNA of the PCK9 protein and changes a single letter from an A to a C and that means that the protein doesn’t work anymore,” Stuart says.
“It changes all the cells in the liver and the body and the way these behave.”
This technology is currently being evaluated in people with genetic abnormalities, he says.
If the technology is successful it means people who had previously had high and dangerous levels of cholesterol can lead normal lives without having to take high doses of daily medication - tablets that still may not get the cholesterol down to levels needed to avoid heart disease.
The same technology can be used to treat haemophilia, by changing a faulty protein to one that works properly, he says.
“This is definitely a very exciting advance in an important area.”
