Gene therapy can reprogram heart muscle cells to act as biological pacemaker

This animation explains how researchers created biological pacemaker cells in pigs using gene therapy. (Courtesy of AAAS/Carla Schaffer)
July 16

Researchers working with pigs have developed a way to treat heart rhythm disorders by genetically transforming muscle cells in a tiny section of the heart into specialized “pacemaker cells.”

“We have been able, for the first time, to create a biological pacemaker using minimally invasive methods and to show that the new pacemaker suffices to support the demands of daily life,” said Eduardo Marbán, director of the Cedars-Sinai Heart Institute and one of the lead authors of the study, published Wednesday in the journal Science Translational Medicine.

The goal of the research is to provide a biological alternative to the traditional pacemaker used to regulate heart rate through electrical pulses.

In the study, 12 pigs with heart block — a condition where the electrical signal is slowed or disrupted as it moves through the heart — were injected with either the single gene to reprogram cells or a fluorescent green protein acting as a placebo.

A virus containing a single gene called TBX18 was injected directly into the area — no bigger than a peppercorn — which normally acts as the heart’s metronome, reprogramming cells to fire electrical impulses that determine and regulate the rhythm of an individual heart.

For two weeks, cardiologists monitored the average heart rate of the pigs at two significant times of the day, during morning feeding and activity and at night when the pigs slept. It was crucial to test whether the reprogrammed cells could regulate the changing rate required to support the pigs’ daily activities.

The therapy is fast-acting, reprogramming enough muscle cells to effectively regulate heart rate within 24 to 48 hours. By the eighth day of testing, the mean heart rate was significantly higher in the pigs that received the gene therapy than that of the control group.

However, at the end of two weeks, the effectiveness of the therapy had waned due to the pigs’ immune systems gradually clearing the virus supporting the gene.

“Long-term experiments are under way to develop a long-term biological pacemaker,” said Eugenio Cingolani, director of the Cardiogenetics-Familial Arrhythmia Clinic at Cedars-Sinai, also an author of the study.

The researchers predict that clinical trials in people could start within three years.

The new therapy could eliminate complications that affect at least 2 percent of all electronic pacemakers, such as infections and functional problems that cause them to fail. The treatment is seen initially as a bridge procedure for patients who need to have their pacemakers removed and eventually replaced.

The treatment could also be used for babies in utero with congenital heart defects that cannot be fitted with a pacemaker and have no alternative therapy available, the researchers said.

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