Overwhelming Evidence of the Beneficial Effects of SERCA Gene Transfer in Heart Failure

To the Editor: We read with great interest the work by O’Donnell et al1 on the possible toxic effect of the sarcoplasmic reticulum Ca2+ ATPase pump in neonatal cardiac myocytes. Because gene transfer of SERCA2a is being currently considered as a modality for the treatment of heart failure,2 the work by O’Donnell et al has the potential of raising concern about such a strategy. However, a number of limitations in this study preclude any definitive conclusions regarding the toxicity of overexpressing SERCA. The authors demonstrated the expression of the noncardiac isoform SERCA1 in embryonic and neonatal cardiac myocytes in their studies. These cardiomyocytes have a poorly developed sarcoplasmic reticulum and do not represent functionally the adult heart. In addition, the expression of the SERCA1 isoform may result in abnormal intracellular trafficking, which results in …