Chemotherapy drug could be repurposed to treat fatal heart failure, computer model suggests

A chemotherapy drug used to fight bone-marrow cancer also has the potential to treat and prevent potentially deadly heart failure, a powerful new drug-screening tool developed at UVA Health suggests.

Chemotherapy drug could be repurposed to treat fatal heart failure, computer model suggests
In heart failure, the organ loses the ability to pump adequate blood for the body's needs. This can lead to fatigue, wheezing, weakness, swollen legs and feet and, ultimately, death. Image Credit: UVA Health

The tool was created by University of Virginia researchers Jeffrey J. Saucerman, PhD, and graduate student Taylor G. Eggertsen. The sophisticated computer model suggested the drug midostaurin could help prevent the  enlargement of heart muscle cells that often precedes heart failure, and subsequent lab results bore that out.

While additional human testing is needed, Saucerman says the new computer model has demonstrated great potential for identifying already available drugs that can be repurposed to battle heart failure, a condition affecting millions of Americans.

“This new computer tool helps us find new uses for old drugs, and it also explains how they may work in the heart,” Saucerman said. “New drugs take decades to develop. We hope this tool will help us find drugs for heart failure that are already known to be safe and effective for other diseases ”

Preventing heart failure

Heart failure is a progressive condition – meaning it grows worse with time – in which the heart loses the ability to pump blood. This can lead to fatigue, wheezing, weakness, swollen legs and feet and, ultimately, death. 

While there are drugs used to treat heart failure, more than half of people with the condition die within five years of diagnosis. That speaks to how urgently new and better treatments are needed.

To address this need, Saucerman and Eggertsen created a complex computer model of the harmful growth of heart muscle cells prior to heart failure. This model allowed them to run sophisticated simulations demonstrating how existing drugs would affect that process, known as cardiac hypertrophy.

This approach has identified a number of drugs that show initial promise for heart disease that we would not have suspected.

Taylor G. Eggertsen, Graduate Student, University of Virginia

The researchers screened more than 250 candidate drug and found 38 that slowed the harmful heart changes. Further, the model let the scientists understand how the drugs were having this effect, helping the researchers to winnow down their options. They then tested the most promising drugs in heart muscle cells. They ultimately found that midostaurin, a chemotherapy drug used to treat acute myeloid leukemia, a cancer of the blood and bone marrow, had the potential to slow the damaging changes to the heart.

“Now that we have found interesting drugs in computer simulations and heart muscle cells, we plan to test these drugs in experimental models that are more similar to humans,” said Saucerman, who is part of UVA’s Department of Biomedical Engineering, a joint program of the School of Medicine and School of Engineering. “This computational treasure hunt for drugs may eventually lead to more options for treating heart failure patients.”

Findings published

The researchers have published their findings in BJP, the British Journal of Pharrmacology. The article is open access, meaning it is free to read. Saucerman and Eggertsen have no financial interest in the work.

The research was funded by the National Institutes of Health, grants HL162925, HL160665, HL137755 and HL007284.

Source:
Journal reference:

Eggertsen, T. G., & Saucerman, J. J. (2023). Virtual drug screen reveals context‐dependent inhibition of cardiomyocyte hypertrophy. British Journal of Pharmacology. doi.org/10.1111/bph.16163

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