New research brings new gene therapy for heart failure closer to the clinic

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A stained section of a pig heart treated with the viral vector 33 days after injection. Credit: S. Liu et al., Science Translational Medicine (2021)

Research from Baylor College of Medicine, the Texas Heart Institute, and collaborating institutions is bringing promising new gene therapy to treat heart failure closer to the clinic.

Published in Scientific translational medicine, the study showed that knocking down the hippopotamus signaling pathway in cardiomyocytes in the heart of pigs after they had a , resulted in cardiac tissue renewal and improved function compared to pig hearts in which the hippopotamus signaling pathway was not altered. Given that the heart of the pig is considered a valuable model for studying the , the findings suggest that this it can be useful in treating people .

Heart failure remains the leading cause of death in the Western world, causing more deaths than all cancers combined. The best current treatment for heart failure is one , but the number of hearts available for transplantation is limited, underscoring the need for alternative treatments.

“One of the interests of my lab is to develop ways to heal studying the pathways involved in heart development and regeneration, ”said the corresponding author, Dr. James Martin, professor and chair Vivian L. Smith of Baylor Regenerative Medicine and director of the Texas Heart Cardiomyocyte Renewal Laboratory Institute.







An echocardiogram of the heart and left ventricle, which gradually decreased its function in untreated pigs 104 days after a heart attack. Credit: S. Liu et al., Science Translational Medicine (2021)

Previous work has shown that when patients are in heart failure, it increases the activity of the hippopotamus signaling pathway, which acts to inhibit heart repair. Earlier work by the Martin Laboratory revealed that disabling the Hippo signaling pathway in a mouse model that mimics advanced human heart failure caused murine hearts to regain their pumping function.

“Encouraged by these results, we took the next step by checking whether to disable the Hippo signaling pathway. it would also help the recovery of injured hearts, ”said the first author, Dr. Shijie Liu, a postdoctoral associate at the Martin Laboratory.

An essential first step in translation before bringing gene therapy to humans

In the current study, researchers modeled in pigs what happens in a human patient who has a heart attack and evaluated the effect of the gene. demolition of the hippopotamus signaling pathway in cardiac recovery.







Dr. James Martin, director of the Cardiomyocyte Renewal Laboratory, professor at the Texas Heart Institute and Vivian L. Smith Chair of Regenerative Medicine at Baylor College of Medicine in Houston, Texas, talks about its publication. Credit: © Copyright Texas Heart Institute

“Pigs with a heart attack have a condition similar to that found in a human patient who has a blockage in the main artery of the heart, which leads to a myocardial infarction,” Martin explained. “After in pigs, we administered gene therapy to extinguish the hippopotamus directly into the hearts of pigs. Finally, we compared the effects of therapy or lack of therapy on heart function. “

“We were thrilled with the results,” Liu said. “Three months after treating the pigs, those who received gene therapy had improved their heart function, showed signs that their cardiomyocytes were regenerating, had less fibrosis or scarring, and had evidence that new blood vessels had formed. The procedure was shown to be safe, as the pigs tolerated the therapy very well. “

“Our findings support our goal of moving to clinical trials in humans,” Martin said. “This is a potentially transformative strategy to treat human heart failure. It takes advantage of the heart’s healing ability, favoring the repair of the heart muscle and improving its function, which can make a substantial difference in the lives of those who suffer. attack “.


Scientists are reversing advanced heart failure in an animal model


More information:
S. Liu et al., “Demolition of gene therapy of hippopotamus signaling induces cardiomyocyte renewal in pigs after myocardial infarction.” Scientific translational medicine (2021). stm.sciencemag.org/lookup/doi/ … scitranslmed.abd6892

Citation: New research brings new gene therapy for heart failure closer to the clinic (2021, June 30), retrieved June 30, 2021 at https://medicalxpress.com/news/2021-06- gene-therapy-heart-failure-closer.html

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