Novel drug molecule targets T-cells causing inflammation in heart failure patients

Researchers from the Ohio State University Wexner Medical Center and College of Medicine have developed a new drug molecule that targets T cells that cause inflammation in patients with heart failure, halting further progression of the disease.

During heart failure, T cells, which are part of the immune system, go from protecting the body from infection to causing heart failure. In a study of mice with heart failure, Ohio State University researchers found that these “bad” T cells have elevated levels of a protein called estrogen receptor alpha. With the help of the Drug Development Institute, which is part of the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, researchers have identified and tested a new drug molecule that activates estrogen receptor beta, which known to have an opposite effect on the estrogen receptor alpha. The new treatment stopped the progression of heart failure.

Study results are published today in the journal Circulation Heart Failure of the American Heart Association.

This is an important finding, as no new heart failure drug has been developed in recent years. We know that inflammation plays an important role in worsening heart failure symptoms, but we have not been able to identify appropriate treatments that can target ‘bad’ inflammation without affecting the ‘good’ inflammation. With this drug, we can selectively target ‘bad’ T cells and prevent the disease from getting worse.”


Shyam S. Bansal, assistant professor in the Department of Physiology and Cell Biology and researcher at the Dorothy M. Davis Heart and Lung Research Institute

Heart failure causes chronic inflammation and affects about 6 million Americans, many of whom require a heart transplant, according to the American Heart Association. The two most common causes are high blood pressure and coronary artery disease.

“Currently, there is no treatment that can stop the progression of heart failure. About half of patients die within the first five years of their diagnosis. This new treatment addresses one of the underlying mechanisms of the disease. With this drug, we may be able to improve patients’ longevity significantly, and if we stop the disease early, patients may not even need a heart transplant,” Bansal said.

Ohio State University has patented the drug molecule OSU-ERb-012. Future research plans are to determine the drug’s effectiveness in other animal studies, identify the lowest therapeutic dose, and eventually conduct clinical trials in patients with human heart failure.

The research is funded by the National Institutes of Health’s Heart, Lung and Blood Institute and the Ohio State Drug Development Institute. The investigations were largely conducted by Rachel Rosenzweig and Vinay Kumar under Bansal’s supervision.

Source:

The Ohio State University Wexner Medical Center

Reference magazine:

Rosenzweig, R., et al. (2022) Estrogen receptor β agonists modulate T lymphocyte activation and enhance left ventricular remodeling during chronic heart failure. Circulation: heart failure. doi.org/10.1161/CIRCHEARTFAILURE.121.008997.

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