Experimental drug may slow atherosclerosis inflammation

The researchers analyzed blood samples from 34 men and women with atherosclerotic cardiovascular disease. All participants were taking statins at the time. There were 24 other participants without atherosclerotic cardiovascular disease in the study for comparison.

The scientists determined that the plasma – the liquid part of the blood – from the people with atherosclerosis triggers an unusually high inflammatory signal in blood immune cells.

Rather than try to create a new drug, the researchers looked at a series of datasets with hundreds of thousands of test results and decided to work with saracatinib because of its anti-inflammatory properties.

“While many people are aware of the risks of high cholesterol and heart disease, the role of inflammation in plaque progression and heart attacks and strokes is being increasingly appreciated,” Dr. Jeffrey Tyler, an interventional cardiologist with Providence St. Joseph Hospital in California who was not involved in the study, told Medical News Today.

One expert noted that based on how saracatinib works, there is potential for studying its use against leukemia and atherosclerotic disease.

“It’s important to understand that these studies are in very early stages,” said Dr. Sameer Amin, the chief medical officer and a cardiologist for LA Care Health Plan who was not involved in the study.

“Though a drug may theoretically work to treat a condition, treatments often affect the body in unexpected ways,” Amin told Medical News Today. “This leads to the possibility of drug repurposing but also may mean that medication in development may never work. We need to be rigorous in differentiating theoretical potential from proven clinical benefit.”

The researchers reported that saracatinib reduced inflammatory signaling by about 90% in diseased human cells.

When tested in a rabbit model, plaque-based inflammation was reduced by 97%.

In a mouse model, an 80% decrease in cells associated with inflammation in atherosclerosis was seen.

Additionally, plaques shrunk by between 48% and 70% in the mouse model, depending on the dose of saracatinib used.

“Our study employed an unbiased human systems immunology approach to investigate potential drugs that target the concerted action of multiple molecules involved in inflammation,” said Dr. Chiara Giannarelli, an associate professor of cardiology and pathology at NYU Cardiovascular Research Center at the NYU Grossman School of Medicine who has a patent pending for this therapeutic approach she developed for treating atherosclerosis cardiovascular disease.

“By directly examining inflammation responses in human samples, we discovered that saracatinib can diminish these inflammatory responses,” Giannarelli told Medical News Today.

The researchers noted that the drug positively mitigated inflammation within atherosclerotic lesions.

Experts say it’s too soon to tell if saracatinib can effectively treat atherosclerosis.

“Before a medication establishes itself as a viable form of treatment, it needs to go through multiple levels of testing in large populations to show that it is improving patient outcomes,” Amin said. “There are currently many cardiovascular medications that are in early stages that may never pan out.”

The next step is to test the drug on larger animals, according to Dr. Sanjiv Patel, an interventional cardiologist at MemorialCare Heart & Vascular Institute at Orange Coast Medical Center in California who was not involved in the study.

“In addition, testing needs to be done for the safety of humans. Although other studies tested safety, the researchers need to look at safety based on the dosage they are testing for reducing human inflammation,” Patel told Medical News Today.

The approach used by the researchers at NYU Grossman School of Medicine might work to introduce new treatments for atherosclerosis.

“By combining cutting-edge technologies and computational tools, we can identify promising drug candidates more efficiently,” Giannarelli said. “This streamlined process holds promise for expediting the development of effective treatments and bringing them to market sooner, benefiting individuals with atherosclerosis.”

Atherosclerosis occurs when your arteries become clogged with fatty deposits, known as plaques, according to the Heart and Stroke Foundation.

People can live many years with plaques before they block the artery.

“Initially, there is plaque buildup in the artery, which causes irritation and then inflammation,” Patel said. “When that happens, the body sends additional cells to relieve the irritation. Because of the buildup, these cells also become irritated and inflamed. The body sends more cells to relieve it, and the process starts again.”

“The researchers hope the drug saracatinib can stop the process, which will stop the inflammation,” Patel continued.

Currently, statins are the most used drugs to treat atherosclerosis. There are two sides to treatment.

“Statins target mainly the lipid side,” Dr. Rigved Tadwalkar, a cardiologist at Providence Saint John’s Health Center in California, told Medical News Today. “But they also work to reduce inflammation. So, they are the most effective drugs that target both pathways, which is why they are so widely used.”

“Inflammation can contribute to many different diseases – including atherosclerosis,” Tadwalkar continued. “We can’t just clear out all inflammation. Doing so could cause severe side effects. I think we will end up with two drugs – one that addresses lipids and one that addresses inflammation. But lifestyle factors are also important. Diet and exercise also target both pathways. They reduce cholesterol and improve inflammation.”