While the human heart was once thought incapable of regeneration, growing evidence shows that even the adult heart can grow new cells, albeit slowly. Roger Hajjar, director of the Cardiovascular Research Center at the Mount Sinai School of Medicine, in New York, and Bernhard Kuhn, a cardiologist at Children’s Hospital Boston, aim to harness this regenerative ability to change how heart disease is treated. They cofounded a startup called CardioHeal, based in Brookline, MA, to develop peptide drugs that can spur growth of new heart muscle cells in the human body.
Growing heart muscle: A peptide called neuroregulin1 can stimulate heart muscle cells (red) in rats to divide. Markers of dividing cells (red) are shown in green/yellow. Cell nuclei are shown in blue.
The scientists have identified a pair of peptides that can stimulate new cell growth and improve heart function in rodents induced to have heart attacks. Hajjar’s lab at Mt. Sinai is now testing one of the peptides, periostin, in pigs induced to have heart attacks. Because these animals have hearts similar in size to humans, they provide a good model for testing new therapies prior to human clinical trials. Preliminary results show that injecting the peptide into the pericardium, the lining around the heart, seems to help. “They’re not completely back to normal, but they’re much better,” says Hajjar.
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Researchers hope the molecules will ultimately provide an alternative approach to treating heart disease. Currently, people who suffer a heart attack get medication, such as beta blockers, to make it easier for the heart to beat, and surgery to clear blocked arteries. “But none are directed at giving new heart muscle back after myocardial infarction,” says Kuhn. The cardiologist says patients regularly ask him if the treatment is available for them, part of the reason he decided to found the company. “I’ve been getting patient requests for a couple of years, but we don’t have an open trial or anticipate opening one anytime soon.”
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Cardioheal’s approach is, to some degree, in competition with stem-cell therapy, which is already being tested in humans. Scientists are working on different ways of harvesting and delivering stem cells to patients with heart disease, and clinical trials have so far yielded mixed results. Transplanted cells appear to have difficulty surviving and integrating into their new environment. In fact, some scientists suggests that benefit of cell transplants comes from the cells ability to stimulate innate growth. Triggering this process with peptides “may be a simpler method of treatment of certain conditions such as cardiomyopathy [an enlarged heart] where the problem is lack of viable, contractile heart muscle cells,” says Amish Raval, a cardiologist at the University of Wisconsin, in Madison, who is not involved with the company.
Cardioheal still has a number of questions to address before testing the peptides in patients. “What is the least invasive way of getting it to the patient’s heart?” asks Hajjar. “At what point after heart attack would you deliver this–early, late, when a patient develops congestive heart failure?” Researchers say they haven’t seen adverse effects in treated animals, but extensive safety testing needs to be done before human trials. “Tumor formation, noncardiac muscle tissue formation, causing dangerous arrhythmias needs to be systematically evaluated in animal models with broad dose ranges tested,” says Ravel. “I would be interested in knowing whether the cardiac cells actually integrate with the environment in the heart, or just independently contract. There has to be electrical and mechanical integration for this treatment to work.”
