Biological Pacemaker Developed Using Gene Therapy

Steve Winton, 'Medtronic EnRhythm Pacing System,' via Flickr. CC BY 2.0.

Using gene therapy, researchers have managed to temporarily restore a normal heart rate in pigs with abnormal heart rhythms by reprogramming cardiac muscle cells to act as “biological pacemakers.” The findings suggest that such a technique could one day give rise to an alternative to the traditional, electronic pacemaker. The study has been published in Science Translational Medicine

Our bodies are fitted with a natural pacemaker- the sinoatrial node. This is a bundle of specialized cells located in the right atrium, one of the heart’s four chambers, which send out electrical impulses at regular intervals that trigger the heart muscle to contract and thus pump out blood. In some individuals, these impulses are disrupted and consequently the heart rate is slowed or abnormal.

These patients require electronic pacemakers to be fitted to restore a normal heart rhythm. While these are effective, the surgical procedure required to fit them is invasive, some can go wrong and need replacing, and individuals are also at risk of infection. The generation of an alternative to solve these problems is therefore desirable, which is exactly what a research team led by Eduardo Marbán from the Cedars-Sinai Medical Center have been working on.

The scientists mimicked a serious human heart condition in 12 pigs called heart block which is where the electrical signals fail to spread through the heart. To do this, they destroyed the pacemaking cells of the sinoatrial node with high-frequency radiowaves, which slowed the pigs’ heart rate from 100 beats per minute (bpm) to around 50 bpm.

Next, the scientists injected the pigs’ hearts with a virus called an adenovirus that had been modified to carry either a gene called TBX18 or a control that produced a fluorescent protein. Previous studies had demonstrated that TBX18 can convert heart muscle cells, or cardiomyocytes, into pacemaker cells.

Within just two days, the infected heart cells began expressing pacemaker genes and started to regulate heart rate. The researchers then monitored the heart rate during different activities such as sleeping, moving around or eating to make sure that the new cells could regulate the changing rate required to perform daily activities.

They found that the biological pacemaker activity was sustained for two weeks, regardless of what the pigs were doing, and that pigs injected with the TBX18 gene had a significantly higher heart rate than those injected with the controls.  

According to Marnán, although this approach is simpler than other biological approaches so far trialed, the effects are likely temporary because over time, the immune system will start to attack the virally infected cells. However, the team are monitoring animals that have been receiving treatment over a period of several months to see how long it is tolerated.

Despite the current narrow window of use, the treatment may be useful as a temporary fix in certain scenarios, for example patients that require a pacemaker change due to malfunction or infection. Furthermore, the researchers say that it could be used for fetuses with heart defects that obviously cannot be fitted with a pacemaker, or children that quickly outgrow pacemakers.

The team predicts that if approval is granted by the FDA, human trials could be initiated in as little as 2-3 years. 

[Via NatureScience Translational Medicine and Washington Post]

Header image, "Medtronic EnRhythm Pacing System," by Steve Winton, via Flickr, used in accordance with CC-BY-2.0.

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