Surgery is often life-saving for infants born with heart defects, but doctors have yet to be able to replace heart muscle that is scarred and dysfunctional.
Now researchers hope to overcome that challenge by stimulating regeneration of heart tissue.
Researchers say children born with congenital heart disease are at greater risk of developing heart failure—even after surgical correction of the problem.
Adult medicines don’t work
“It is not surprising that survivors often develop heart failure later on,” says lead author Bernhard Kühn, associate professor of pediatrics at the University of Pittsburgh School of Medicine and director of research for the division of cardiology at Children’s Hospital.
“But when these patients were given adult medicines in clinical trials, it turned out that they were not effective. The need for pediatric-specific heart failure therapies is increasingly recognized.”
For the study, published in the journal Science Translational Medicine, researchers examined the potential of recombinant growth factor neuregulin-1 (rNRG1), which stimulates heart regeneration by driving proliferation of heart muscle cells called cardiomyocytes.
They treated newborn mice with injections of rNRG1 at various times after heart injury and found that early treatment starting the first day after birth boosted cardiomyocyte cell division and heart function, and reduced scarring to a significantly greater degree compared to treatment that began at five days after birth.
Encourage the heart
The growth factor also drove cardiomyocyte proliferation in lab tests of heart muscle samples obtained during surgery from human infants with congenital heart disease.
“These findings suggest that rNRG1 administration in infants with these birth defects might be a new therapeutic strategy for pediatric heart disease,” Kühn says.
“Delivering agents early on that encourage the heart to make new cardiomyocytes could help the heart perform normally and reduce the risk of developing heart failure later in life.”
More research needs to be done before clinical testing of this strategy, the research team says.
Other researchers from University of Pittsburgh Medical Center, Boston Children’s Hospital, Beth Israel Deaconess Medical Center, Bosch Institute, and the Institute of Molecular Biotechnology of the Austrian Academy of Sciences collaborated on the study. Kühn began the research while a member of the faculty at Boston Children’s Hospital.
The National Institutes of Health, Boston Children’s Hospital, and the Richard King Mellon Foundation Institute for Pediatric Research at Children’s Hospital of Pittsburgh of UPMC funded the work.
Source: University of Pittsburgh