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First biologic pacemaker created by gene therapy in guinea pigs

Working with guinea pigs, Johns Hopkins scientists have created what is believed to be the first biologic pacemaker for the heart, paving the way for a genetically engineered alternative to implanted electronic pacemakers. The advance, reported in the Sept. 12 issue of Nature, uses gene therapy to convert a small fraction of guinea pigs' heart muscle cells into specialized "pacing" cells.

"We now can envision a day when it will be possible to recreate an individual's pacemaker cells or develop hybrid pacemakers -- part electronic and part biologic," says Eduardo Marbán, M.D., Ph.D., Michel Mirowski professor at Hopkins' Institute of Molecular Cardiology, adding that clinical applications are still a few years away.

"Most applications of gene therapy try to cure a disease caused by a single defective or missing gene, but we used the cells' genes as a tool box to tweak its function," adds Marbán. "This is akin to turning a clunky old car into a hot rod -- if you have the parts and expertise, it can be done."

In the Hopkins experiments, heart cells in the guinea pigs spontaneously and rhythmically "fired" after the scientists genetically altered the cells' balance of potassium. Such a "biopacemaker" is a potentially important option for patients at too high a risk for infection from implanted electronic pacemakers or too small for an implanted device, say the researchers. "A biologic pacemaker should also be able to adjust to the body's changing needs, whereas an electronic pacemaker, at least in its simplest form, does not," says Marbán. "Anything that normally makes our heart go pitter-pat doesn't change the steady rhythm of the electronic pacemaker. Instead, people get tired very quickly."

Two tiny sets of "pacing" cells in the heart normally give the organ its regular beat by stimulating other cells to contract. If these specialized cells stop working or die, an implanted electronic pacemaker can
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
11-Sep-2002


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