Gene Therapy Can Restore Function to Failing Heart Cells
Dec. 6, 1999 (Atlanta) -- Researchers announce that they have successfully restored function to weak, inefficient heart muscle cells from patients with end-stage congestive heart failure. The team gave the failing cells extra copies of the SERCA2a gene that produces a protein vital to normal heart muscle function but lacking in sick hearts. The findings are presented in today's issue of Circulation: Journal of the American Heart Association.
"Congestive heart failure is a growing health problem in the U.S., especially as the population ages," study leader Roger J. Hajjar, MD, tells WebMD. "Aging induces changes in the heart that make it stiffer and more prone to congestive heart failure [CHF]." In addition, he says, medical conditions such as coronary artery disease and uncontrolled high blood pressure can also cause heart failure. Although heart failure is "reversible to a certain degree" in limited cases, for many people "treatment slows the process but does not really reverse it or treat it," says Hajjar.
Over the past 10 years, Hajjar's team has been "unraveling the molecular mechanisms" of CHF in an attempt to find better treatments. Through their work and that of others, it is known that calcium is critical to a strong, healthy heartbeat. When heart muscles contract, calcium stored in the sarcoplasmic reticulum -- structures surrounding each muscle fiber -- is expelled into the cytosol, or cell interior. When the muscles relax, the calcium is returned to the sarcoplasmic reticulum by a protein pump called SERCA2a. In heart failure, says Hajjar, this pump malfunctions, "causing calcium to be handled abnormally."
In their early experiments, Hajjar inserted the gene that controls SERCA2a production into normal heart cells. "We found that if you overexpress [add extra copies of] this gene, the cell contracts better, faster, stronger," he tells WebMD. Next, they gave the SERCA2a gene to animals with heart failure, and found that "compared to the animals that did not receive the gene, survival was definitely better," he says.
In their most recent study, Hajjar's team delivered the gene to cells from diseased hearts that had been removed from 10 transplant patients. "We found that we were able to restore contractile function back to that of normal cells," says Hajjar. Compared to untreated cells from the sick hearts, the treated cells contracted faster, relaxed faster, and calcium levels were restored to normal. A failing cell has only 20% of its contractile function, but "when you overexpress this SERCA2a gene, you restore 70-100% of normal function. It's quite significant." What's more, he tells WebMD, when they "made the cells beat faster and faster," which would normally kill a failing heart cell, the transfected cells still responded like healthy heart cells.
Gene Therapy Can Restore Function to Failing Heart Cells
Dec. 6, 1999 (Atlanta) -- Researchers announce that they have successfully restored function to weak, inefficient heart muscle cells from patients with end-stage congestive heart failure. The team gave the failing cells extra copies of the SERCA2a gene that produces a protein vital to normal heart muscle function but lacking in sick hearts. The findings are presented in today's issue of Circulation: Journal of the American Heart Association.
"Congestive heart failure is a growing health problem in the U.S., especially as the population ages," study leader Roger J. Hajjar, MD, tells WebMD. "Aging induces changes in the heart that make it stiffer and more prone to congestive heart failure [CHF]." In addition, he says, medical conditions such as coronary artery disease and uncontrolled high blood pressure can also cause heart failure. Although heart failure is "reversible to a certain degree" in limited cases, for many people "treatment slows the process but does not really reverse it or treat it," says Hajjar.
Over the past 10 years, Hajjar's team has been "unraveling the molecular mechanisms" of CHF in an attempt to find better treatments. Through their work and that of others, it is known that calcium is critical to a strong, healthy heartbeat. When heart muscles contract, calcium stored in the sarcoplasmic reticulum -- structures surrounding each muscle fiber -- is expelled into the cytosol, or cell interior. When the muscles relax, the calcium is returned to the sarcoplasmic reticulum by a protein pump called SERCA2a. In heart failure, says Hajjar, this pump malfunctions, "causing calcium to be handled abnormally."
In their early experiments, Hajjar inserted the gene that controls SERCA2a production into normal heart cells. "We found that if you overexpress [add extra copies of] this gene, the cell contracts better, faster, stronger," he tells WebMD. Next, they gave the SERCA2a gene to animals with heart failure, and found that "compared to the animals that did not receive the gene, survival was definitely better," he says.
In their most recent study, Hajjar's team delivered the gene to cells from diseased hearts that had been removed from 10 transplant patients. "We found that we were able to restore contractile function back to that of normal cells," says Hajjar. Compared to untreated cells from the sick hearts, the treated cells contracted faster, relaxed faster, and calcium levels were restored to normal. A failing cell has only 20% of its contractile function, but "when you overexpress this SERCA2a gene, you restore 70-100% of normal function. It's quite significant." What's more, he tells WebMD, when they "made the cells beat faster and faster," which would normally kill a failing heart cell, the transfected cells still responded like healthy heart cells.
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