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  • Nov 23, 2014
  • Updated: 10:53am
NewsWorld
MEDICINE

US scientists use gene therapy to create biological heart pacemaker

Research using hearts of sick pigs marks major advance in developing a biological alternative to electronic devices commonly fitted in humans

PUBLISHED : Thursday, 17 July, 2014, 9:07pm
UPDATED : Friday, 18 July, 2014, 3:35am
 

No batteries required: scientists are creating a biological pacemaker by injecting a gene into the hearts of sick pigs that changes ordinary cardiac cells into a special kind that induces a steady heartbeat.

Their new study represents a big step towards developing an alternative to implanted electronic pacemakers.

"There are people who desperately need a pacemaker but can't get one safely," said Dr Eduardo Marban, director of the Cedars-Sinai Heart Institute in Los Angeles in the US state of California, who led the work. "This development heralds a new era of gene therapy" that one day might offer them an option.

A human heartbeat depends on a natural pacemaker, a small cluster of cells - about the size of a peppercorn, Marban says - that generates electrical activity.

Called the sinoatrial node, it acts like a metronome to keep the heart pulsing at 60 to 100 beats a minute or so - more in an active person. If that node quits working correctly, hooking the heart to an electronic pacemaker works very well for most people.

But about 2 per cent of recipients developed an infection that required the pacemaker to be removed for weeks until antibiotics wiped out the germs, Marban said. And some fetuses were at risk of stillbirth when their heartbeat faltered, a condition called congenital heart block.

For over a decade, teams of researchers have worked to create a biological alternative that might help those kinds of patients, trying such approaches as using stem cells to spur the growth of a new sinoatrial node.

Marban's newest attempt uses gene therapy to reprogramme a small number of existing heart muscle cells so that they start looking and acting like natural pacemaker cells. Because pigs' hearts are so similar to human hearts, the team studied the approach in 12 laboratory pigs with a defective heart rhythm.

They used a gene named TBX18 that plays a role in the embryonic development of the sinoatrial node. Working through a vein, they injected the gene into some of the pigs' hearts - in a spot that does not normally initiate heartbeats - and tracked them for two weeks.

Two days later, treated pigs had faster heartbeats than control pigs who did not receive the gene, the researchers reported in the journal Science Translational Medicine. That heart rate automatically fluctuated, faster during the day. The treated animals also became more active, without signs of side effects.

"In essence, we created a new sinoatrial node," Marban said. "The newly created node takes over as a functional pacemaker, bypassing the need for implanted electronics and hardware."

It's a different type of gene therapy, and a few other genes that might switch one cell type to another were under early study to treat deafness and diabetes, Marban said.

It was not clear how long these newly reprogrammed cells would keep working, cautioned doctors Nikhil Munshi and Eric Olson of the University of Texas Southwestern Medical Centre, who were not involved in the research but analysed the findings in a journal commentary.

Also, the gene was delivered by putting it into a virus engineered to disappear relatively soon afterwards. The Texas pair noted that some virus particles landed in the lung and spleen, and that longer studies are needed to rule out safety concerns.

Still, the results "provide an encouraging indication that a biological pacemaker might eventually be ready for human translation", Munshi and Olson concluded.

The heart rate did start to slow a little towards the study's end, but Marban said there was no reason to believe "that the two weeks is somehow a magic cap. We have every reason to believe that this could go on longer".

He said longer-term animal studies were under way, and he hoped to begin first-step human studies in about three years.

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