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Factor identified that makes treating aging hearts with gene therapy difficult

Scientists at Massachusetts General Hospital (MGH) and their colleagues have found why older cardiac cells are more difficult to treat with gene therapy than younger cells. The findings, published in the May 4, 2003, issue of Circulation, have implications for therapeutic strategies aimed at the aging population.

"Efforts to develop gene therapy for heart disease have been geared towards the elderly since they have fewer therapeutic options," says principal investigator Roger Hajjar, MD, of the Cardiovascular Research Center at MGH. "Our results show that we have some hurdles to overcome in order to optimize treatments in this population."

The researchers found that gene transfer by adenovirus is less efficient in aging rat heart cells than in cells from their younger counterparts. Over the years, adenoviruses have been used in laboratory and clinical research to deliver beneficial genes into their target cells. These modified viruses rely on several proteins on the surface of cells in order to gain entry and deliver therapeutic genes.

Hajjar's group had previously shown that aging cells are more resistant to entry by adenovirus than adult cells, but it had not been clear why. Through detailed laboratory experiments, the research team found that crucial proteins called integrins, which sit just under a cell's membrane, are scarce in older cardiac cells. It turns out that adenoviruses need these integrins to get into cells.

"The adenovirus binds to a receptor on the outside of a cell that is linked to integrins below the cell's surface," says Hajjar, who is an associate professor of Medicine at Harvard Medical School. "The receptor itself is abundant in older cells, but the integrins are deficient."

This may sound like bad news for the elderly, but Hajjar points out that it is possible to boost the expression of integrins. "The next step is to devise different ways of stimulating integrins specifically so you can still u
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
3-Mar-2003


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