Experimental Cancer Drug Shows Potential in Slowing Inflammation Associated with Heart Disease

In a groundbreaking discovery, scientists have found that saracatinib, an experimental drug initially investigated for its potential in treating various diseases, may have the ability to significantly reduce inflammation linked to atherosclerosis—a condition that contributes to heart disease. While saracatinib has demonstrated promising results in diminishing plaque-based inflammation and reducing plaque deposits in animal models, further clinical trials are necessary to confirm its effectiveness in human patients.

A novel therapeutic opportunity arises through the “reverse-engineering” of an existing compound.

According to a recent study conducted by researchers at NYU Grossman School of Medicine, this experimental drug, previously explored for potential treatments against cancer, lung diseases, and Alzheimer’s disease, has the potential to slow down the progression of atherosclerosis, a major factor in the development of heart disease.

The study delves into the underlying mechanisms of atherosclerosis, a condition characterized by the accumulation of fatty deposits within blood vessels. These deposits can solidify into plaques, triggering inflammatory reactions that disrupt normal blood flow and increase the risk of severe cardiovascular events like heart attacks and strokes.

Published on June 8 in the journal Nature Cardiovascular Research, the study revealed that plasma from individuals with atherosclerotic disease elicited an abnormally high inflammatory response in blood immune cells. Further investigations demonstrated that saracatinib reduced this inflammatory signal by more than 90% in both human blood samples and diseased tissue samples.

Dr. Letizia Amadori, a senior research scientist at NYU Langone Health and co-lead author of the study, stated, “Our findings provide new insights into the inflammatory mechanisms underlying atherosclerosis and suggest that saracatinib may be an effective therapy when standard treatment with statins fails to yield positive outcomes.”

While physicians often prescribe statins to lower harmful fats in the blood, studies have shown that inflammation persists in many patients even after reducing plaque deposits, placing them at continued risk of heart attacks. The reasons behind this chronic immune response in patients are not yet fully understood, and current anti-inflammatory treatments often prove ineffective.

To conduct the study, the research team analyzed blood samples from 34 individuals—both men and women—with a specific condition known as atherosclerotic cardiovascular disease (ASCVD), all of whom were already taking statins. These samples were compared with those from 24 healthy donors.

In an effort to identify saracatinib, the researchers examined 4,823 genes, including 277 genes already known to be involved in inflammation and the production of cytokines and other proteins that sustain a chronic immune response.

The team speculated that if a specific medication could prevent the production of all these molecules, it could potentially suppress the immune response. Rather than starting from scratch, the researchers explored a list of approved or investigational pharmaceuticals. They accessed datasets from the National Institutes of Health, specifically the Library of Integrated Network-Based Cellular Signatures, which contains a vast array of test results documenting the effects of various molecules, signaling proteins, and genetic changes on human cells.

Since saracatinib demonstrated the ability to reverse the expression of target genes—the process responsible for protein production—the authors conducted tests on human cells, diseased tissue, and animal models to evaluate whether it could effectively halt, slow down, or reverse inflammation associated with ASCVD.

The results of the study revealed that saracatinib obstructs the activity of genes responsible for producing inflammatory proteins such as interleukin-1 beta and interleukin-6, which contribute to immune reactivity in ASCVD. It is worth noting that a previous trial demonstrated the effectiveness of an interleukin-1 beta inhibitor in preventing heart attacks. Additionally, the drug enhanced the expression of genes known to produce proteins that aid in the removal of plaque deposits by transporting fats away from the arteries.

Further experiments conducted on rabbits indicated that saracatinib reduced inflammation caused by plaque deposits by approximately 97% compared to untreated animals. In mice, the same therapy resulted in an 80% reduction in cells associated with plaque inflammation and decreased plaque deposits by 48% to 70%, depending on the dosage of the medication, according to Dr. Amadori.

Dr. Chiara Giannarelli, MD, Ph.D., senior author of the study and associate professor in the Departments of Medicine and Pathology at NYU Langone, expressed optimism about the team’s “reverse-engineering” approach to discovering new applications for existing drugs. She stated, “This method has the potential to uncover therapies for virtually any disease involving inflammation since these chemicals have already undergone safety testing, offering a rapid and cost-effective pharmaceutical development approach.”

Dr. Giannarelli added that while saracatinib holds promise, it still requires clinical testing to ensure its efficacy as a treatment for patients.

The study received funding from National Institutes of Health (NIH) grants.

Dr. Giannarelli has filed a patent for this therapeutic approach to treat ASCVD, as well as for the team’s drug development pathway. The terms and conditions of the patent are being managed in accordance with the policies and practices of the Icahn School of Medicine at Mount Sinai and NYU Langone Health.

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More about inflammation

• Study: Systems immunology-based drug repurposing framework to target inflammation in atherosclerosis – The original study published in Nature Cardiovascular Research.
• NYU Langone Health – Official website of NYU Langone Health, the institution where the research was conducted.
• National Institutes of Health (NIH) – The NIH provided grants for funding the study.
• Library of Integrated Network-Based Cellular Signatures – Information about the dataset used in the study for exploring the effects of various molecules and genetic changes on human cells.