TY - JOUR T1 - New insights into SERCA2a gene therapy in heart failure: pay attention to the negative effects of B-type natriuretic peptides JF - Journal of Medical Genetics JO - J Med Genet DO - 10.1136/jmedgenet-2017-105120 SP - jmedgenet-2017-105120 AU - Yuting Zhai AU - Yuanyuan Luo AU - Pei Wu AU - Dongye Li Y1 - 2018/02/24 UR - http://jmg.bmj.com/content/early/2018/02/24/jmedgenet-2017-105120.abstract N2 - Sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a) is a target of interest in gene therapy for heart failure with reduced ejection fraction (HFrEF). However, the results of an important clinical study, the Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) trial, were controversial. Promising results were observed in the CUPID 1 trial, but the results of the CUPID 2 trial were negative. The factors that caused the controversial results remain unclear. Importantly, enrolled patients were required to have a higher plasma level of B-type natriuretic peptide (BNP) in the CUPID 2 trial. Moreover, BNP was shown to inhibit SERCA2a expression. Therefore, it is possible that high BNP levels interact with treatment effects of SERCA2a gene transfer and accordingly lead to negative results of CUPID 2 trial. From this point of view, effects of SERCA2a gene therapy should be explored in heart failure with preserved ejection fraction, which is characterised by lower BNP levels compared with HFrEF. In this review, we summarise the current knowledge of SERCA2a gene therapy for heart failure, analyse potential interaction between BNP levels and therapeutic effects of SERCA2a gene transfer and provide directions for future research to solve the identified problems. ER -