A drug that acts like a vaccine has been shown to lower “bad” cholesterol or LDL and reduce the amount of fatty plaque that can lead to heart attacks. The drug rallies the immune system against a molecule that contributes to atherosclerosis.
The drug, called AT04A, is a form of immunotherapy that targets an enzyme, called PCSK9, that contributes to the formation of harmful plaque in coronary arteries.
In studies of mice fed fatty, Western-style diets putting them at risk for heart disease, researchers showed that AT04A reduced the total amount of cholesterol by 53 percent and shrank atherosclerotic plaques by 64 percent, according to Oliver Siegel, who is with the Austrian pharmaceutical company AFFiRiS.
“More importantly in the mice, we have seen a very significant reduction in development of those plaques, said Siegel. “As a result, we believe the reduction of LDL which we have seen before would translate into a clinical benefit, i.e. reduction of plaque that would otherwise reduce inflammation that would otherwise be the cause of heart attack potentially.”
AT04A was able to rally the immune system to produce antibodies that blocked the PCSK9 enzyme in the circulation of mice during the study.
The study was published in European Heart Journal.
The immunotherapeutic approach, according to Siegel, is similar to, but not a vaccine per se in the sense that it doesn’t target bacteria and viruses, just the harmful enzyme.
In an accompanying editorial in the journal, Ulrich Laufs of Saarland University in Germany and Brian Ference of the University of Bristol noted that in people taking cholesterol-lowering drugs, including AT04A, there may be an increased risk of patients developing diabetes.
But Siegel said nothing like that has cropped up so far in studies of the compound.
The authors of the editorial wrote in the short term, having a long-acting, cholesterol lowering drug may far outweigh the slight risk of new onset diabetes.
Currently, many people with high levels of cholesterol take daily medication that drives down “bad” LDL cholesterol; but, Siegel says compliance is less than ideal.
“What a few studies have shown is that patients, who…have already had a heart attack, have a relatively low adherence or compliance rate and we would imagine that patients who didn’t have a heart attack would have an even lower compliance rate,” said Siegel.
Fatty plaques that develop in the heart vessels can choke off the flow of blood, causing a heart attack. If a piece of plaque breaks off and travels to the brain, it can cause stroke. Diseases of the coronary arteries are a leading cause of illness and death worldwide.
Siegel said the shot under the skin would have to be given once a year like an immunization.
Early human clinical trials testing the compounds safety are nearly completed, and Siegel hopes to have a cholesterol-lowering, clot-busting drug on the market in the next few years.
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