"Fixing this one problem corrects a large number of abnormalities in the heart," say principal authors Federica del Monte MD, PhD, and Roger Hajjar, MD, of the Cardiovascular Research Center at MGH. The MGH scientists have been studying a molecular pump that regulates calcium flow and allows the heart to contract and relax. "Heart failure in the aging is due to the fact that this pump is abnormal. It doesn't allow the heart to relax and fill appropriately," says Hajjar.
Del Monte and Hajjar's team used a model system in which laboratory rats develop symptoms similar to those of humans with heart failure. The researchers discovered that fixing the calcium pump through gene replacement significantly improved survival. "We found that four weeks after we treated these rats with the gene encoding the calcium pump, the survival was 63 percent compared to 9 percent for rats that didn't receive the gene," says Hajjar.
The scientists also found that the energetic state of the heart was improved with this gene therapy. This is important because the heart requires a continuous supply of energy, and energy levels are low in patients with heart failure.
Del Monte and Hajjar are excited about the possibilities of their new findings. In the past, pharmacological agents designed to increase the strength of the heart led to an increased mortality in patients. Those drugs are not prescribed any more, and there has been a great need for alternative heart failure treatments. The improved rat survival rates in this study offer hope for a potential option. This novel method of molecularly targeting a gene within cardiac cells has the potential to alter treatments for patients with cardiovascular diseases. Preclinical trials are underway with large animals, and Hajjar is hopeful that treatment strategies will reach the clinics within a couple of years.
Other researchers involved in the study include Eric Williams, Djemal Lebeche, PhD, Ulrich Schmidt, MD, PhD, Anthony Rosenzweig, MD, Judith Gwathmey, VMD, PhD, and E. Douglas Lewandowski, PhD.
The study was supported by the National Institutes of Health, the Doris Duke Charitable Foundation and the American Federation of Aging.
The Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $300 million and major research centers in AIDS, the neurosciences, cardiovascular research, cancer, cutaneous biology, photomedicine, transplantation biology. In 1994, the MGH joined with Brigham and Women?s Hospital to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups and non acute and home health services.