Scientists led by Walter Koch, Ph.D., director of the Center for Translational Medicine in the Department of Medicine in Jefferson Medical College of Thomas Jefferson University in Philadelphia, used a virus to insert the gene for a protein called S100A1 into failing rat hearts. "In contrast to other gene therapy strategies geared to overexpressing a gene," says Dr. Koch, who is W.W. Smith Professor of Medicine at Jefferson Medical College, "because this protein is reduced in heart failure, simply bringing the protein level back to normal restored heart function." Dr. Koch and his co-workers report their findings December 1, 2004 in the Journal of Clinical Investigation.

S100A1, which is part of a larger family of proteins called S100, binds to calcium and is primarily found at high levels in muscle, particularly the heart. Previous studies by other researchers showed that the protein was reduced by as much as 50 percent in patients with heart failure. A few years ago, Dr. Koch and his co-workers put the human gene that makes S100A1 into a mouse, and found a resulting increase in contractile function of the heart cell. The mice hearts worked better and had stronger beats.

Dr. Koch's Jefferson team now examined whether it could make failing hearts normal again. The researchers 12 weeks after they simulated a heart attack in the rats delivered the human S100A1 gene to the heart through the coronary arteries by injection of a genetically-modified common cold virus as a carrier. After about a week, they found the hearts began to work normally. In addition, the animals' heart muscle showed improved efficiency in using its energy supply, which was decreased in heart failure. According to Dr. Koch, the improvements were seen in both the whole animal as well as in individual heart cells.

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1-Dec-2004