Genetically-engineered heart cells may be able to replace the electronic pacemakers that hundreds of thousands of cardiac patients have transplanted each year, suggests a new study in guinea-pigs.
In a healthy heart, the rhythm is orchestrated by a small group of cells called the sinoatrial (SA) node. But Eduardo Marb谩n of the Johns Hopkins University School of Medicine in Baltimore, Maryland and his colleagues found that ordinary cardiac cells can generate their own beat if a single protein is knocked out by gene therapy.
The researchers are now planning to repeat the experiment in pigs. 鈥淭hey are large enough that we can use the same off-the-shelf clinical tools and imaging machines that we would use for patients,鈥� says Marb谩n . If all goes well, clinical trials could start in less than five years, he asys.
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鈥淚t鈥檚 a very interesting new direction that we didn鈥檛 have yesterday, for a common problem,鈥� says Peter Spooner, a cardiology researcher at the National Institutes of Health near Washington, DC.
鈥淒istinct advantages鈥�
Unlike prosthetic pacemakers, Marb谩n 鈥榮 bioengineered ones respond to biochemical signals that naturally control the heart鈥檚 rate, Spooner points out. So during exercise, they would speed up. They would also not need batteries and would grow with the patient. 鈥淭hose are distinct advantages,鈥� he says.
In the developing embryo, each cell of the heart can spontaneously maintain a beat by itself. But in the adult heart, the cells become specialised. Those in the SA node produce specialised proteins, while the genes for other proteins fall silent.
As a result, only this tiny group of cells sparks the beginning of each contraction, while other cells fall in line and respond to those steady electrical jolts.
Clogged channel
One of the inactive genes in the SA node is the Kir2 family of genes, which encodes proteins for a channel for positively-charged potassium atoms. When potassium flows, it squelches other electronic signals, repressing spontaneous beats.
So Marb谩n s team wondered if clogging the channel could by itself restore the ability of ordinary heart muscle cells to keep the beat.
They designed a poisoned form of one Kir2 protein that blocked the potassium channel and genetically-engineered it into a virus. The team then injected this virus into the lower heart chamber of normal guinea pigs. Individual cells that took up the virus began a whole new rhythm, about 5 per cent faster than cells in the SA node.
More remarkably, in animals where groups of adjacent cells received the virus, the hearts of the animal took up this new, quicker pace. 鈥淲e had injected the virus randomly, so we didn鈥檛 expect to see this very often,鈥� says Marb谩n . 鈥淏ut it happened 40 per cent of the time. That鈥檚 pretty remarkable.鈥�
His team is now investigating if adding more SA-node-specific genes to the cells will 鈥渢une鈥� the cells down to the perfect, physiological rhythm.
Journal reference: Nature (vol 419, p132)