Pacemakers are remarkable devices that save the lives of 300,000 people in the U.S. each year. They essentially take over for failing hearts, but since the devices require invasive surgery to implant in the heart, researchers have been looking for less invasive approaches to keeping the heart ticking. And now, reporting in the journal Science Translational Medicine, Dr. Eduardo Marban, director of the Cedars-Sinai Heart Institute, has a lead—thanks to pigs.
“We were able for the first time to create a biological pacemaker using minimally invasive methods, and show that the new pacemaker cells suffice to support the demands of daily life,” he said. “When the pigs exercised, the hearts beat faster. When they were at rest, their hearts slowed down.”
He and his colleagues say that a single gene can transform existing heart cells to take over the function of ailing pacemaker cells in the heart, The group tested their theory in mice, and were encouraged enough by the results to predict that human trials may be as close as three years away.
Marban has been working for more than a decade to find a better way to keep pacemaker patients’ hearts pumping at the right rate. In particular, he was focused on the 2% of them who need to go on antibiotics to treat an infection—because the devices are foreign objects implanted into the body, infections are possible—and in the interim have their pacemakers removed to be cleaned. During that time, these patients receive a temporary pacing device connected to a catheter, but the catheter itself may be an additional source of infection and make the antibiotic treatment less effective.
In Marban's experiment, he simply loaded deactivated cold viruses, which are able to easily infect cells, with a gene—called TBX18—that is active during fetal development but later shuts off. Earlier studies showed that simply bathing cells in TBX triggered normal heart cells to start morphing into the ones that keep hearts working. That’s exactly what happened in the seven pigs whose hearts were injected with the gene. A small proportion of their normal heart cells, the size of a peppercorn, were transformed into electrically pulsing cells and essentially took over the pacemaker function of the pigs’ hearts.
Dr. Eugenio Cingolani, director of the cardiogenetics-familial arrhythmia clinic at Cedars Sinai and a co-author of the paper, said that while encouraging, more studies on the efficacy of the genetic reprogramming process, as well as a more in-depth analysis of the potential adverse effects are needed.
But the findings represent a promising first step toward a potentially new technique for treating certain life-threatening conditions.
“This development heralds a new era in gene therapy, where genes are used not only to correct deficiency disorders but to convert one cell to another to treat disease,” said Marban. “Now that we and others are hot on the trail of developing therapeutics based on this principle of cell reprogramming, I anticipate that the flood gates will open and people will look for genes of interest to do whatever they want in particular organs or tissues of interest.”
At the very least, he believes that a hardware-free, biological pacemaker based on the technique could become reality.