Researchers have successfully used a gene therapy procedure to turn ordinary cardiac muscle cells in pigs into specialised ones that deliver a steady heartbeat.
The therapy could become an alternative to implanted electronic pacemakers in the future, they report in the journal Science Translational Medicine.
“We have, for the first time, been able to create a biological pacemaker using minimally invasive methods and show that the biological pacemaker supports the demands of daily life,” says study co-author Dr Eduardo Marbán, director of the Cedars-Sinai Heart Institute in Los Angeles.
The research involved pigs with a condition called heart block that makes their hearts beat too slowly.
By injecting a human gene into a tiny region of the heart’s pumping chambers roughly the size of a peppercorn, the researchers reprogrammed heart muscle cells into a type of cell that emits electrical impulses to drive the beating heart, restoring the pigs’ heart rate to normal.
The procedure achieved the same result as implanting an electronic pacemaker that sends electrical pulses to the heart if it beats too slowly or skips a beat.
“This development heralds a new era of gene therapy where genes are used not only to correct a deficiency disorder but actually to convert one type of cell into another to treat disease,” says Marbán.
The technique, which the team has previously studied in rats, is the culmination of a dozen years of research.
While not as precise as the previous rat studies, pig hearts are very similar to human hearts and allow the researchers to study the overall safety and functional efficacy of the technique.
Study co-author Dr Eugenio Cingolani, director of the institute’s Cardiogenetics-Familial Arrhythmia Clinic, says “if all goes well” in further animal studies examining the procedure’s long-term effectiveness and safety, “we hope to be able to begin trials in humans within three years.”
The researchers envision using the procedure initially to help people with heart rhythm disorders who cannot use a pacemaker because of device-related complications like an infection or in fetuses in the womb with congenital heart block.
Such fetuses cannot have a pacemaker implanted and risk severe heart failure often resulting in stillbirth. The researchers hope to develop an injection-based treatment to deliver the gene therapy to these developing babies.
In the future, the procedure might be used in a broader patient population as a realistic alternative to the pacemaker, say the researchers.
“Rather than having to undergo implantation with a metallic device that needs to be replaced regularly and can fail or become infected, patients may someday be able to undergo a single gene injection and be cured of the slow heart rhythm forever,” says Cingolani.
Using a minimally invasive catheter procedure, the researchers injected pigs that had complete heart block with a gene called TBX18 that is responsible for a protein that makes the heart keep the right rhythm.
On the second day after the gene was injected, the pigs developed a faster, more normal heartbeat that lasted for the rest of the 14-day experiment.
The researchers used a common type of virus called an adenovirus to introduce the gene into the pigs, but say the virus poses minimal risk.