Patients suffering from arrhythmias, or irregular heartbeats, might one day be able to restore their heart's normal rhythm with the injection of a single gene. The experimental gene stimulates the creation of a natural heart pacemaker, doing away with the need for an implanted electronic device to regulate the heartbeat. The technique could be a major step forward in the quest for new, biological therapies to treat heart disease.
Researchers at Cedars-Sinai Heart Institute in Los Angeles created biological pacemaker cells by inserting a single gene, called Tbx18, into a virus and injecting the engineered virus into the hearts of guinea pigs bred to have arrhythmia.
The gene prompts the creation of an exact replica of a raisin-sized node in the heart’s upper right chamber which normally maintains regular heart rhythms. Tbx18 transformed heart muscle cells, called cardiomyocytes, into a colony of natural pacemaker cells.
Institute director, Eduardo Marban says this sino-atrial node, called S-A-N, is a tiny island of 10-thousand cells among the roughly 10-billion cells comprising the heart muscle. He says the new S-A-N created by the inserted gene is virtually identical to the structure it replaces.
“If we were to give scientists who are specialized in this area the data to look at it and compare it to a genuine pacemaker cell -- which, as I said, are exceedingly rare -- to the ones we created by putting a gene in an ordinary heart cell, they would be hard-pressed to tell the difference,” Marban said.
Marban estimates that five to six billion dollars is spent each year worldwide on electronic pacemakers for millions of patients. But artificial pacemakers have potentially serious drawbacks. The implanted devices can cause life-threatening infections and every five to seven years, the batteries that operate them must be changed, requiring surgery.
Also, Marban notes, the externally programmed devices do not work properly for all patients, while others are too sick to use them.
In about two years, Marban says researchers plan to conduct human trials of their gene therapy with the sickest heart patients to prove the biological therapy is both safe and effective.
“Basically, what we are going to look for are patients who already have an electronic pacemaker, who develop a severe infection and need to have the electronic pacemaker taken away. And during the time the patients are free of an electronic pacemaker, their hearts need to be sustained by some means, and we hope we would be able to create this biological pacemaker to keep the heart going between treatments,” Marban said.
It could still be several years, however, before the biological therapy becomes an option for all heart patients in need of pacemakers.
An article on the creation of a natural cardiac pacemaker is published in the journal Nature Biotechnology.