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Patrick Guilfoile: Using a virus to make a heart pacemaker

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About 3 million people are currently living with an electronic pacemaker in their chest, and surgeons implant 600,000 new pacemakers each year. Heart pacemakers can be a lifesaving treatment, but they require a significant medical intervention, are expensive, and the batteries eventually wear out.

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Physicians use electronic pacemakers when a person’s natural heart rhythm is altered or unstable. Normally, in the heart, a patch of about 10,000 specialized cells acts as a biological pacemaker, and regulates the beating of the other 5,000,000,000 heart muscle cells. Sometimes, due to age, genetic disease, or infection, these specialized cells become impaired and the heart then beats too slowly or irregularly. An electronic pacemaker can take over the function of these impaired cells, and get the heart to beat more normally.

Since the pacemaker cells in the heart originate during fetal development from normal heart cells, scientists have been interested in learning whether it is possible to create a new biological pacemaker in the heart, if the old one stops ticking. Initial attempts to do this included genetic modification of the heart muscle cells to respond to different electrical currents, but this approach didn’t pan out. Other attempts to regenerate heart pacemaker cells involved the use of embryonic stem cells. But only some of the heart cells generated from embryonic tissue were pacemaker cells, and implanted embryonic cells may sometimes develop into tumors, so an alternate strategy was investigated. In a recent paper, scientists from the Cedars- Sinai Heart Institute in Los Angeles described experiments where they added an active master control gene to heart muscle cells.  Their initial experiments involved isolated heart cells from rats, grow in dishes in the laboratory. The researchers succeeded in getting these regular heart cells to behave and look like normal pacemaker cells, when the cells contained the added gene.

The next step was to attempt to make this change happen in a living animal. The scientists packaged the “pacemaker gene” in a virus that causes respiratory infections. The virus was disabled so it could no longer cause disease, but was still able to act as a guided missile to insert the gene into heart muscle cells.  The researchers injected the virus with a needle and syringe directly into the heart muscle cells and they found that nearly 10 percent of the cells at the area of injection converted to pacemaker cells. These cells had all the natural pacemaker cell functions, and could be induced to beat faster or slower using natural hormonal signals.

We are likely a long way from the time when an electronic pacemaker will be replaced with a needle full of viruses. However, this research shows the power of genetic techniques in helping us better understand how our bodies work, and potentially developing more effective treatments using that knowledge. 

More information is available in “Direct conversion of quiescent cardiomyocytes to pacemaker cells by expression of Tbx18”, by Nidhi Kapoor, Wenbin Liang, and others, Nature Biotechnology(2012) doi:10.1038/nbt.2465 Published online 16 December 2012.

PATRICK GUILFOILE has a Ph.D. in bacteriology and is currently an interim associate vice president at Bemidji State University.

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