Gene Therapy May Play Role in Reversing Heart Failure

NEW YORK, Dec 06 (Reuters Health) - Gene therapy can reverse life-threatening heart failure, reports a team of researchers from the United States and Great Britain.

Heart failure, where the weakened heart muscle can no longer pump enough blood to supply the body's needs, is a common cause of disability and death worldwide. "Heart failure continues to be a growing health problem in the United States, especially as the population ages," the team notes. Treatment now consists mainly of drugs that slow the progression of heart failure, without reversing the process itself. Heart transplant is a cure, but many patients are not candidates, and donor organs are scarce.

In a potential breakthrough, the new study shows that failing heart muscle cells loaded with a gene called SERCA2a began acting normally again, contracting more rapidly and powerfully, according to lead author Dr. Roger J. Hajjar.

His team's findings are published in the December 7th issue of Circulation: Journal of the American Heart Association.

"This ability to modify the contraction of failing human cardiac cells represents an important step toward gene therapy for heart failure," Hajjar, of Massachusetts General Hospital in Boston, said in a news release. "And by confirming the role the SERCA2a protein plays in heart failure, we now have a molecular target for other therapeutic approaches."

It has been well established that heart failure is associated with problems moving calcium in and out of heart cells, an important problem because this movement of calcium helps to control the contraction of cells that give the heart its pumping action. SERCA2a plays a key role in pumping calcium out of heart cells, making cells more sensitive to calcium molecules as they rush back in to start another contracting cycle. A deficiency in SERCA2a was believed to play a key role in heart failure, but it was unknown if replacing the protein would help treat heart failure.

To learn if an increase in SERCA2a can help failing heart cells, Hajjar and colleagues harvested muscle cells from 10 failed hearts removed from patients who received heart transplants. The team injected these heart cells with a virus carrying the gene that makes SERCA2a. These viruses, called vectors, are able to carry genes into cells, ensuring that the gene becomes part of the cell's genetic code.

"Within 24 hours of receiving the gene, which induced overproduction of the SERCA2a protein, the cells from failed hearts began beating and contracting at levels very similar to those seen in cells from normal hearts," according to a statement issued by Massachusetts General Hospital. Additionally, the levels of circulating calcium appeared normal in cells that had the extra gene copies.

"These results support the premise that gene-based therapies and targeting of specific pathways in human heart failure may offer a new modality for the treatment of this disease," the investigators conclude. But the authors also caution that more research is needed to see if improving the ability of heart cells to contract leads to an improvement in symptoms and better survival for heart failure patients.

Circulation: Journal of the American Heart Association 1999;100:2308-2311.
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