Assistant Professor-in-Residence
Division of Cardiology, Electrophysiology Section
Cedars-Sinai Medical Center Heart Institute

Project title: Biological Pacemaker in a Pre-Clinical Model of Heart Block

Eduardo Marbán, MD, PhD - Cedars-Sinai Medical Center
Sumeet Chugh, MD - Cedars-Sinai Medical Center
Hee Cheol Cho, PhD - Cedars-Sinai Medical Center

Multidisciplinary Expertise:
Cellular biology, molecular biology, gene therapy, cellular electrophysiology, clinical cardiac electrophysiology, cellular mechanisms of arrhythmias

Project Description:
Abnormally slow heart rhythms affect many people in the USA, and those numbers are steadily increasing as the population ages. While electronic pacemakers are the mainstay of therapy for these conditions, complications from device implantation, such as life-threatening infections, may occur. As an alternative to electronic devices, we propose to study select biological pacemaker candidates in a pre-clinical model, and to develop the most promising candidate as a potential therapeutic agent for first-in-human application.
Gene-based BioP were first described more than a decade ago; somatic gene transfer of various constructs has shown to create BioP activity. However, until recently, in-vivo preclinical applications have been mostly limited to highly-invasive open-chest models. We have developed a clinically-realistic minimally-invasive delivery technique and used it to create BioP in a porcine model of complete heart block. We propose to use this approach to compare two “finalist” therapeutic candidates with fundamentally different mechanisms of action.