Revolutionizing cardiovascular medicine: targeted therapies for the cardiac conduction system
Daniel J. Garry, … , Demetris Yannopoulos, Tamas Alexy
Daniel J. Garry, … , Demetris Yannopoulos, Tamas Alexy
Published October 17, 2022
Citation Information: J Clin Invest. 2022;132(20):e164192. https://doi.org/10.1172/JCI164192.
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Commentary

Revolutionizing cardiovascular medicine: targeted therapies for the cardiac conduction system

Abstract

Arrhythmogenic cardiovascular disorders are associated with considerable morbidity and mortality. Whether cardiac conduction disease is caused by genetic defects, procedural perturbations, valvular disease, ischemia, aging, or heart failure, new therapies are warranted. In this issue of the JCI, Goodyer et al. used state-of-the-art technologies to image the cardiac conduction system (CCS) in real time and to deliver targeted therapies to the CCS and its subcomponents. These findings advance the ability to image and treat specific lineages within the adult heart with the potential for broader applications in the treatment of cardiovascular diseases.

Authors

Daniel J. Garry, Demetris Yannopoulos, Tamas Alexy

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Figure 1

Imaging and targeting the CCS in the adult heart.

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Imaging and targeting the CCS in the adult heart. Goodyer and colleagues...
Goodyer and colleagues generated dye-conjugated antibodies against cardiac conduction–restricted proteins. mCntn2-800 (or mNptn-800) injected intravenously into mice provided a robust signal in adult heart, allowing for live visualization of the CCS. Engineered antibodies that recognize CCS-specific proteins could also deliver targeted compounds to modulate conduction. An anti–human CNTN2 antibody coupled with the cellular toxin saporin (hCNTN2-Sap) resulted in conduction abnormalities, while mCntn2-800 and mNptn-800 did not disrupt the CCS, as measured by ECG. Isolation of single cells from different CCS regions followed by scRNA-seq revealed cell surface markers that might be used to visualize specific parts of the CCS or conjugated with therapeutic cargo to treat cell-specific conduction anomalies (4).