Editors' ChoiceCardiophysiology

Young at heart: Restoring cardiac function in children

Science Signaling  07 Apr 2015:
Vol. 8, Issue 371, pp. ec89
DOI: 10.1126/scisignal.aab2806

When children with heart disease were given adult medicines in clinical trials, the results were disappointing, illuminating the need for pediatric-specific treatment regimens. In adult mice, the recombinant growth factor neuregulin-1 (rNRG1) stimulates heart regeneration by driving the proliferation of cardiomyocytes. Because young mice have more proliferation-competent cardiomyocytes than do adult animals, Polizzotti et al. asked whether rNRG1 put cardiomyocyte proliferation into overdrive if given to mice during the neonatal period. Indeed, newborn mice subjected to heart injury after birth that were treated with rNRG1 starting at 1 day of age showed increased cardiomyocyte cell division, improved heart function, and reduced scarring relative to treatment regimens that began at 4 days after birth. rNRG1 also stimulated cardiomyocyte proliferation in heart muscle isolated from human infants with heart disease who were less than 6 months of age, but not in tissue from older pediatric patients. These findings suggest that rNRG1 administration during the neonatal period might be a therapeutic strategy for pediatric heart disease.

B. D. Polizzotti, B. Ganapathy, S. Walsh, S. Choudhury, N. Ammanamanchi, D. G. Bennett, C. G. dos Remedios, B. J. Haubner, J. M. Penninger, B. Kühn, Neuregulin stimulation of cardiomyocyte regeneration in mice and human myocardium reveals a therapeutic window. Sci. Transl. Med. 7, 281ra45 (2015). [Abstract]