Hardware-Free Cardiac Pacing for Adult and Pediatric Patients with Congenital Heart Disease
Abstract
Topic Area: This project addresses the Topic Area of Congenital Heart Disease. We will directly address Areas of Encouragement by (1) developing cardiac tissue engineering approaches to restore native heart rhythm, (2) allowing for the patient’s own cardiac tissue growth, and (3) preventing or eliminating the need for risky re-operations. Critical Problems To Be Addressed: Congenital heart diseases affect nearly 1 in 100 live born infants. One of the most common complications in these complex and medically fragile patients are heart rhythm abnormalities. All current treatments require implanting a pacemaker, which consists of a battery-operated generator and pacing leads. These devices have a finite end-of-life (maximum of 9-11 years), which becomes substantially shorter for congenital heart disease patients due to their faster heart rate and complete dependence on external pacing. Indwelling hardware requires multiple, invasive surgeries to replace the pacemaker generator and/or the pacing leads. Risks of complications increase with each successive pacemaker and lead replacement. There is no adequate pacemaker therapy for patients with congenital heart diseases. For adult patients, these problems may be tolerable. For pediatric patients, however, these problems are far from tolerable, and largely inadequate as evidenced by up to 85% of mortality rates in infants with congenital heart diseases. Overview of the Proposed Project: We propose to develop biological pacemakers as alternatives to implantable cardiac pacing devices. Powered by our proof-of-concept studies, we will select a lead product candidate from three therapeutic modalities for hardware-free cardiac pacing. For the first time in the field of biological pacemaker, we will perform direct comparison of the three gene transfer modalities for superior cardiac pacing function and wider safety net, all tailored for congenital heart disease patients. Each therapeutic modality will be optimized in a small animal model for maximum safety profile and cardiac pacing function and will then be tested for feasibility in a clinically relevant, large animal model of complete heart block. Ultimate Applicability and Impact of the Research: The ability to improve the lives of these patients using a single-dose, focal gene therapy will change the way cardiac pacing is managed in the clinic. Nearly all of the current research regarding rhythm management in these patients is focused on miniaturizing the current devices. In contrast, this project is innovative in that we seek to restore the patient’s own pacemaker tissue and eliminate all indwelling hardware. There are more than 300,000 pacemakers implanted each year in the U.S. alone, fueling a $5.4 billion global industry for cardiac pacing. This technology will serve dual purposes, one that immediately benefits congenital heart disease patients and the other that can provide therapeutic alternatives to civilian patients with implantable electronic pacemakers. It is also important to note that spontaneous electrical stimulation underlies the basic mechanism of a natural heartbeat. The same principle drives gastrointestinal motility, deep brain stimulation, sleep apnea, obesity/appetite control, or under/over-active bladder control. Thus, the genetic/cell/tissue engineering principles developed from this technology can immediately lead to innovative therapeutic development for non-cardiac diseases as well.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010643
Entities
People
- Hee Cheol Cho
Organizations
- Emory University
- United States Army