Biological Pacemaker Created in Pigs With Gene Therapy

biological pacemaker
A biological pacemaker was created in the hearts of pigs using gene therapy. Specifically, heart cells called cardiomyocytes were converted into pacemaker cells that could be used to control the rate of heartbeats. If this research effort achieves its goal, it could mean that humans who need pacemakers would not need to have a mechanical device implanted but would only need to have cells in their heart transformed to provide the electrical pulses needed to make the heart pump.

In a normal, healthy heart, cells signal the heart muscle to contract and pump the blood throughout the circulatory system. In an unhealthy heart, this function can be slowed or the heartbeats can become irregular. A mechanical pacemaker is then sometimes implanted to make the heartbeats regular. A conventional mechanical pacemaker must be implanted under the skin with surgery. It controls the rate of heartbeats by emitting electrical pulses to the muscles of the heart. Infection, however, is often a complication with conventional pacemakers.

Gene therapy is a procedure where genes (or segments of DNA) are inserted into a cell and the cell then takes up the gene and incorporates it into its own genome. Any cells that are reproduced from the original cell will contain the inserted gene as well. The gene that was transferred into the cardiomyocyte cells was TBX18, which stands for embryonic transcription factor T-box 18. The TBX18 gene is known to play a role in heart development. The gene TBX18 is activated briefly in the sino-atrial node of the hearts of developing embryos, and therefore, this gene may play a role in the creation of rhythm-generating cells. The carrier for the gene was a modified virus and this modified virus was injected into the muscle of the heart.

The reason this gene therapy approach to create a biological pacemaker was carried out in a pig is a pig’s heart is very similar to a human heart. The potential use of pig hearts in human heart transplants has been a consideration in research efforts for a while.

During the research experiment, after the cardiomyocytes were transformed, the pigs were tested on how they responded to physical activity. Results showed the heart rates increased when the pigs exercised and slowed when the pigs rested, which confirmed the biological pacemaker was working.

The creation of a biological pacemaker will circumvent the problems of conventional, mechanical pacemakers. It is unknown, however, what potential complications there might be with biological pacemakers in which cells are “reprogrammed” with gene therapy. Since this procedure involves the insertion of a foreign virus into cells, the immune system may respond and try to destroy the cells. This would mean the biological pacemaker would be short-lived.

The research article reporting the creation of the biological pacemaker was published in Science Translational Medicine. The research was carried out at Cedars-Sinai Heart Institute in Los Angeles, California, as well as at the Taipei Veterans General Hospital and National Yang-Ming University in Taipei, Taiwan. Drs. Eduardo Marban and Eugenio Cingolani were the lead scientists working on the project. It has been reported that this method for creating a biological pacemaker would not be taken to the Food and Drug Administration (FDA) for clinical trials for at least three years.

By Margaret Lutze

See GLV article Health News: Guardian Liberty Voice Daily Digest for July 16, 2014

Sources:
Science Translational Medicine
Nature
New York Times

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