Researchers have discovered a way to use a virus to re-program heart cells and create an all-natural pacemaker that might some day be able to take the place of mechanical pacemakers.
The heart’s normal rhythm is set by the sinoatrial node (SA node) located in the upper part of the heart. This area is known as the pacemaker.
It fires and sends electrical signals through other specialized cardiac cells that allow the heart to contract in its normal fashion. The cells in the SA node that do this job are called pacemaker cells, and they differ from the other cardiac cells, the cardiomyocytes, contract when stimulated and cause the pumping action of the heart.
If something happens to the SA node (disease, injury or something similar), other cells in the heart’s conduction system can take up the job and cause the heart to contract. But the SA node can easily change the speed with which the heart beats, faster when exercising, slower when resting.
The cells that take over the task when the SA node is injured can often only cause the heart to beat at slower rates than normal, even during times of exercise or stress. Sometimes they beat they generate is so slow that the patient is very limited in what he can do. Essentially, the heart rate has an effect on blood pressure. With a too slow heart rate (bradycardia), not enough blood gets pushed out to the areas of the body that need it most. This can cause the patient to become faint or dizzy even at rest, depending on the heart rate that is being maintained. If the patient needs to get up and walk, the remaining pacemaker cells can’t fire fast enough to maintain the perfusion of the tissues with blood. The patient can become more symptomatic and may even die.
Decades ago, electronic pacemakers were developed to be implanted in these patients. The pacemaker can produce a heart rate that can prevent symptoms from occurring. It’s a real lifesaver for many patients. But there are drawbacks. Pacemaker leads (electrodes) have to be implanted in the heart wall. And the pacemaker itself has to be placed in the chest wall surgically. The pacemaker sometimes has to be reprogrammed, its battery may need replaced, the leads may need to be repositioned, and there are other technical problems that can occur. Of course, having a natural pacemaker that can adjust the heart’s rate as needed would be better.
Researchers have now demonstrated that they can replace the damaged natural pacemaker with a pacemaker that is induced in the animal’s own heart.
Scientists damaged the SA node in a number of pigs. This caused the pigs’ heart rates to drop from a normal, of about 100 beats per minute (BPM) down to about 50 BPM. The researchers had engineered a virus that contained a gene (TBX18) that would cause cause cardiac myocytes (non-pacemaker muscle cells) to become pacemaker cells. They injected the virus solution into the pigs’ hearts. Within 48 hours the pigs started having more rapid heart rates. The heart rate varied appropriately when the pigs went from resting, to eating to walking around. So, in effect, the scientists effectively created new biological pacemakers in these pigs. It seems, however that the pacemakers induced this way are temporary. The pigs’ immune system will gradually attack the new pacemaker cells because the immune cells sense that the new pacemaker cells are infected with virus. Right now, the investigators are seeing just how long they can maintain the induced pacemakers with repeated injections of the gene-virus combination.
If the rejection of the new pacemaker area can be prevented, this could allow for a patient to develop his own pacemaker and not have to live with a mechanical one. But, even if the virus-gene induced pacemaker can’t be protected and eventually dies off, it can still be useful. For example, in fetuses who have bradycardia and can’t be given pacemakers in utero. Or take the case of young children, who need pacemaker changes because they are growing quickly. This technique might prove valuable there. Or in critically ill patients who might have increased risk for a pacemaker change until they become more stable.
The investigators will submit their results to the FDA, and if the FDA approves, they may be able to start human trials within a few years.