Pacemaker Cells and Heart Rhythm

Synchronous Pacing from Gene-Induced Biological Pacemakers

The adult human heart beats almost 100,000 times a day. The heartbeat sustains life, and needs no conscious effort in wakefulness or sleep. The heart rhythm is dictated by a small number of specialized cells in the heart, called the pacemaker cells. They initiate each and every heartbeat. The pacemaker cells are akin to the conductor of an orchestra; without them the heart loses its rhythm. Cardiovascular diseases can disturb the heart rhythm, resulting in abnormally slow heart rate. Every year, about 600,000 people are implanted with electronic pacing devices, fueling a $4.5B global industry for cardiac rhythm management devices.

Heart Beat

Aging and/or congenital heart defects could cause the pacemaker cells to malfunction, leading to bradyarrhythmias, which means abnormally slow heart rhythm. The only treatment is implantation of an electronic pacing device which consists of a battery-run generator and electrical lead wires. Although these implantable pacing devices are common and mostly effective, they are fraught with complications. For example, the generator needs to be changed when the battery runs out, the leads could dislodge or break, or the frequency of device-related infection keeps increasing, which requires removal of the entire device. These problems are amplified in pediatric patients who are too small for existing pacemaker devices.

Over the past 12 years, Hee Cheol Cho, PhD, an associate professor at the Wallace H Coulter Department of Biomedical Engineering at Emory and Georgia Tech and the Emory Department of Pediatrics, and his team have been developing device-free approaches to pace the heart. They discovered that an embryonic gene, TBX18 which figures prominently during the formation of pacemaker cells in the embryo, can convert ordinary heart muscle cells into new pacemaker cells. Their published work demonstrate the proof of this concept in which small and large animal models were employed to test biological cardiac pacemakers without the help of electronic pacing devices.

Hee Cheol Cho (sixth from left) and his team
Hee Cheol Cho and his team

In a series of new work, Cho and his team refined their technology to achieve persistent, long-term pacing by combining TBX18 with an inhibitor of TGF-beta signaling. The new findings push the boundary of this concept closer to clinical reality. With funding from the NIH, NSF, the American Heart Association, Georgia Research Alliance, Urowsky and Sahr families, and a Coulter Translational Award, Cho and his team are gearing up to test long-term biological pacemakers in a clinically-relevant, minimally-invasive porcine model of complete heart block. “We believe our technologies have matured sufficiently to draw up a roadmap toward a first-in-human clinical trial in the next few years,” says Cho. Raj Guddneppanavar, the Emory Office of Technology Transfer Licensing Associate working with Dr. Cho said, “This invention, if realized, could change the way heart rhythm is managed for both adult and pediatric patients. We are very excited about this technology and look forward to their continued development toward the clinic.”

Returning to the orchestra metaphor, Cho and his team may be able to give patients back the conductor of their heart rhythm in place of an electronic metronome to keep the tempo of their heart’s song.

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