Pacemakers could be passé with new genetic therapy

A new genetic technique developed by Israeli researchers could enable individuals with heart problems to forgo the use of pacemakers to keep their heart pumping, replacing the electrical device with light-sensitive genes injected into the heart that use flashes of blue light to pace the heart.

The new method for cardiac pacing and resynchronization was developed by Prof. Lior Gepstein and Dr. Udi Nussinovitch of the Technion-Israel Institute of Technology’s Rappaport Faculty of Medicine, and Rambam Medical Center. Results of a study of the method were published this month in the journal Nature Biotechnology.

Pacemakers have undoubtedly saved many lives, but they are not without risks. Some 3 million people are walking around with the devices, and chances are most would be dead if they didn’t have one. Using electrical signals delivered by electrodes attacked to the heart, the device monitors the heart’s natural beat, and if it does not detect one within a specific time, it delivers a short low voltage pulse to “wake up” the heart. More advanced devices go beyond simple beat monitoring and keep track of body temperature, adrenaline levels, etc., pacing the heart to match physical exertion.

But pacemakers aren’t a perfect solution. Problems associated with pacemakers include infections, mechanical failure, dislodging, and other issues. The new method allows users to skip the pacemaker altogether – and avoid the surgery required to insert one.

“Our work is the first to suggest a non-electrical approach to cardiac resynchronization therapy,” Gepstein said. “Before this, there have been a number of elegant gene therapy and cell therapy approaches for generating biological pacemakers that can pace the heart from a single spot. However it was impossible to use such approaches to activate the heart simultaneously from a number of sites for resynchronization therapy.”

The use of light to stimulate genes has been researched for years as part of a field called optogenetics, in which light is used to control neurons that have been genetically developed to be sensitive to light. Most use of the method is still experimental, but the method shows a great deal of promise. In one study, for example, optogenetic stimulation of the spine in deaf mice enable them to hear again. Researchers working in the field have been taking light-sensitive genes from algae and placing them in cells where they act like a switch, turning certain behaviors on or off when the cells are exposed to pulses of light.

The Technion-Rambam experiment was done on rats. The researchers injected one of these algae genes (channelorhodopsin-2) into a specific area of rat heart muscle. The scientists then showed that the light-sensitive protein expressed at this site could be turned on with flashes of blue light and drive the heart muscle to contract. By altering the frequency of the flashes, Gepstein and Nussinovitch could control and regulate the heart rate. They went on to deliver the gene to several places in the heart’s pumping chambers, and demonstrated the ability to simultaneously activate the heart muscle from many places in an effort to synchronize the heart’s pumping function.

Scientists will need to do more research for this optogenetic-based pacemaker strategy to become a reality in human health, Gepstein said. For instance, the gene injected in the rat experiments is sensitive to blue light, which has poor tissue penetration potentially limiting its utility in large animals or humans.

“This means that the affected cells have to be relatively superficial–near the surface of the heart–and that an optical fiber should be implanted bringing the illumination beam as close as possible to the cells,” Gepstein said. “A potential solution in the future may be the development of similar light-sensitive proteins that will be responsive to light in the near-red or even infra-red spectrum, which penetrates tissue much better, allowing illumination from a long distance.”

“This is a very important proof-of-concept experiment, which for the first time, demonstrates a mechanism to pace the heart without the need for wires and allows for simultaneous pacing from multiple sites,” said Dr. Jeffrey Olgin, chief of the Division of Cardiology and co-director of the Heart and Vascular Center at the University of California, San Francisco.

“The most common site of failure of current pacemakers are the leads or wires that connect the heart muscle to the electrical impulse. The approach demonstrated in this paper has the potential to eliminate these wires or have a single lead excite multiple sites simultaneously.”