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Once we're born, our heart muscle has very little growth capacity, nowhere near enough to fix a severe cardiac injury. But researchers in Children's Cardiovascular Program, led by Bernhard Kühn, MD, are developing a toolkit of treatments that would allow the heart to regenerate and strengthen after a heart attack, in patients with heart failure and in children with congenital heart defects, such as hypoplastic left heart syndrome and tetralogy of Fallot.
In 2007, Kühn and colleagues showed that the heart's dormant regenerative capacities can be reawakened. By placing a sponge-like patch over the site of cardiac injury, soaked in a compound called periostin (found in fetal hearts and injured skeletal muscle), they got mature heart muscle cells to start dividing and multiplying in rats. The heart's structure became more normal, and its pumping ability increased (as measured by cardiac ejection fraction). The team has since shown similar benefits in larger animals.
In July, Kühn reported an even more promising regenerative agent, a growth factor called neuregulin1 that is present in the developing heart and nervous system. Unlike periostin, it can be given systemically, avoiding the need to open the heart to place a patch (in mice, it was injected into the abdominal cavity). As reported in the journal Cell, it acts on the same biological pathway as periostin, with similar results.
Kühn envisions a time when patients will receive monthly infusions to build up their hearts. With support from Children's Translational Research Program, he's begun studying heart muscle samples from children undergoing cardiac surgery at the hospital, to see if they respond to the same regenerative factors. Ultimately, he plans to do clinical trials, starting with periostin, in children with heart failure due to congenital heart disease—for whom a heart transplant is often the only treatment.
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