Reading Inflammation to Identify Heart Disease Drugs

Heart disease and stroke caused by atherosclerosis remain the leading causes of death worldwide. Yet research on this form of heart disease has yet to fully explore the link between atherosclerotic cardiovascular disease (ASCVD) and inflammatory stress. In an innovative study by NYU and Mount Sinai Hospital researchers, a creative reverse-engineering method was used to identify the inflammation signature of ASCVD, match a drug candidate, and successfully treat non-human animals.

ASCVD is a gradual condition characterized by plaque accumulation along the arteries' inner walls. This sticky substance impairs blood flow, raises blood pressure, and can lead to the narrowing of arterial walls (angina). Shockingly, statistics indicate that approximately half of Americans aged 45 to 84 may have atherosclerosis without even realizing it. The consequences of ASCVD can range from chest pain (angina) to blood clots, heart attacks, or strokes.

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Several clinical trials have explored repurposing existing anti-inflammatory drugs, originally designed for rheumatic arthritis, in ASCVD patients. However, the results have shown modest improvements. The authors of this Science Translational Medicine study suggest that general anti-inflammatory treatments can't target the complex immune alterations that occur during ASCVD.

To overcome these challenges, researchers developed an innovative ex vivo screening method. They exposed blood cells to plasma from ASCVD patients and evaluated the inflammatory response. The ASCVD plasma induced monocyte white blood cells and dendritic immune cells' activation and generated a unique inflammatory signature. By comparing this data with existing datasets, the researchers identified a cancer drug called saracatinib, currently being developed by AstraZeneca, that showed potential in reversing this specific inflammatory response.

As Senior author Chiara Giannarelli, MD, Ph.D., explains, "Our reverse-engineering method of finding new uses for old drugs can in theory be harnessed to uncover therapies for practically any disease that involves inflammation" (via EurekAlert). The best part of this drug identification method is "since these chemicals have already been tested for safety, this technique offers a swift and cost-effective approach to pharmaceutical development."

Repurposing the cancer drug saracatinib has demonstrated the potential to reverse the specific inflammatory response associated with ASCVD. With further research and clinical trials, this innovative approach could pave the way for effective therapies for ASCVD, benefiting patients worldwide. Streamlined clinical trials examining the effect of saracatinib on ASCVD should be forthcoming.

Sources: NIH, Nature Cardiovascular Research, EurekAlert!