Jefferson Scientists Use Gene Therapy to Rescue Failing Hearts in Animals

Close to 5 million Americans have heart failure and more than 400,000 new cases are being diagnosed each year. While the overall death toll from heart disease has declined, the number of people dying from chronic heart failure continues to rise.

Now, in an encouraging scientific development, heart researchers at Jefferson Medical College (JMC) of Thomas Jefferson University in Philadelphia have used gene therapy to bring failing rat hearts back to normal.

Jefferson scientists led by Walter Koch, PhD, Director of the Center for Translational Medicine in the Department of Medicine, used a virus to insert the gene for a protein called S100A1 into failing rat hearts. 

“Because this protein is reduced in heart failure, simply bringing the protein level back to normal restored heart function," says Dr. Koch, who is also W.W. Smith Professor of Medicine at JMC. 

“This is a remarkable rescue and reversal of cardiac dysfunction, with obvious clinical implications for future heart failure therapy. We have a unique molecule necessary for normal heart function.”

Dr. Koch and his co-workers reported their findings December 1, 2004 in the Journal of Clinical Investigation. 

Crucial Part of Process for Heart Beat
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. 

S100A1 is also found in the cell’s energy-producing mitochondria, Dr. Koch adds. He thinks the protein may be a link between energy production and calcium signaling in the heart cell – a crucial part of the process that makes the heart beat. 

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. Twelve weeks after they simulated a heart attack in the rats, the researchers 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 muscles showed improved efficiency in use of energy supply, which was decreased in heart failure. According to Dr. Koch, the improvements were seen in the whole animal as well as in individual heart cells.

What’s Next
Next, Dr. Koch and his colleagues hope to learn more about the mechanisms behind S100A1’s actions, and eventually, develop gene therapy protocols in humans.