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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 Hospital Boston’s Cardiovascular Program, led by Bernhard Kühn, MD, are developing a toolkit of treatments to encourage heart muscle to regenerate and strengthen after a heart attack, in patients with heart failure and in children with congenital heart defects. These defects include hypoplastic left heart syndrome and tetralogy of Fallotófor which a heart transplant is often the only treatment.
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). In rats, as mature heart muscle cells started dividing and multiplying, the heart’s structure became more normal and pumping ability increased. Since then, the team has shown similar benefits in larger animals.
In the July 24 issue of Cell, Kühn describes an even more promising treatment: a growth factor called neuregulin1 found in the developing heart and nervous system. It acts on the same biological pathway as periostin, with similar results, but unlike periostin, can be injected systemically, avoiding the need to open the heart to place a patch.
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 studying heart muscle from children undergoing cardiac surgery to see if it responds 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.
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