A Gene Therapy to Promote Cardiomyocyte Proliferation Improves Late Stage Heart Failure in Rats

Researchers have developed a gene therapy that upregulates of Cdk1 and Cdk4 in heart muscle. These genes provoke cardiomyocytes into replication, and this has been shown to improve function in the context of heart failure. Here, researchers show that this can help to improve heart function even comparatively late into the development of progressive heart failure, broadening the number of patients who can potentially benefit once this reaches the clinic.

Heart failure remains the leading cause of mortality in the U.S. During a heart attack blood stops flowing into the heart. Without oxygen, part of the heart muscle dies. The heart muscle does not regenerate, instead it replaces dead tissue with a scar made of cells called fibroblasts that do not help the heart pump. If there is too much scarring, the heart progressively enlarges, or dilates, weakens and eventually stops working.

In a previous study, researchers successfully used gene therapy to improve acute cardiac dysfunction in animals. Their method effectively and specifically delivered genes that promote proliferation to heart cells, generating new heart muscle. This approach not only strengthened the heart improving its ability to keep the blood flowing, but also prevented typical subsequent congestion in the liver, kidneys, and lungs in rats and pigs. "In this study, we did something that had not been done before. We intervened with the same gene therapy but not during acute heart failure or early in the disease as in our previous experiments, but late in the disease during the chronic phase four weeks after cardiac injury had severely damaged the heart."

Four months after treating the animals, the researchers checked cardiac function and heart structure. "We were surprised to see evidence of significant heart cell proliferation, a marked reduction in scar size and a significant improvement in cardiac function. Although heart dilation and lung congestion associated with chronic heart failure were not improved, the treatment partially improved liver and kidney functionality."

Link: https://blogs.bcm.edu/2024/02/13/from-the-labs-not-too-late-to-repair-gene-therapy-improves-advanced-heart-failure-in-animal-model/

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