Gene Therapy Creates Pacemakers in Guinea Pigs

Using gene therapy, scientists have been able to convert a small fraction of heart muscle cells in guinea pigs into specialized "pacing” cells that work like biologic pacemakers, paving the way for a genetically engineered alternative to implanted electronic pacemakers. The research was reported in the September 12, 2002, issue of Nature.

In most heart muscle cells, a special channel maintains a balance of potassium that makes it more difficult for them to "fire,” so instead of generating electricity on their own, they must be triggered by pacemaker cells. When these cells stop working or die, an implanted electronic pacemaker can keep the heartbeat going.

Scientists at Johns Hopkins University (Baltimore, MD, USA; www.jhmi.edu) decided that altering the potassium balance might allow heart cells to regain the ability to fire without being triggered. They attached the gene for a defective potassium channel to a virus, adding green fluorescent protein so infected cells could be easily identified, and injected the gene-carrying virus into the heart muscle of guinea pigs. Three to four days later, the heart cells had begun to make the defective potassium channel, and a new, faster pace-setting impulse was clearly visible on electrocardiograms from the animals.

"We've created a biologic pacemaker in the guinea pig, but now the hard work comes,” says Eduardo Marban, M.D., Ph.D., professor at Hopkins' Institute of Molecular Cardiology. "We need to fine tune it: develop controlling strategies, find the optimum place to re-engineer the cells in the heart, and control the frequency of the new pacemaker.”




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