Gene Therapy Problem Pinpointed

Older cells may be more resistant to viruses carrying help for heart failure

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HealthDay Reporter

MONDAY, Feb. 3, 2003 (HealthDayNews) -- Here's the dream: An older person is dying of heart failure, as his or her aging heart muscles gradually lose the ability to pump blood. Those muscle cells can be reinvigorated by sending in young genes, packed in harmless adenoviruses.

Here's the problem: It's unexpectedly difficult to get those helpful adenoviruses into older cells, much more difficult than getting them into younger cells.

Here's the newly discovered reason, published in the March 4 issue of Circulation: Older cells have a deficiency of little-known proteins called integrins, which sit just under the cell membrane and facilitate the entry of one substance or another. Now researchers working on gene therapy for heart failure may have a way to make the idea work.

The deficiency of integrins in older cells could be a defense mechanism, says Dr. Roger Hajjar, associate professor of medicine at Harvard Medical School and a researcher at the Massachusetts General Hospital.

"We feel that the aging person has an immune system that is less robust," he says. "A decrease in viral uptake is a way to protect an older person from viral infection."

Hajjar believes it may be possible to boost the activity of integrins, so that fewer adenoviruses can be used when gene therapy becomes a reality. Keeping the viral dose low is desirable because too much could have a toxic effect on patients, particularly older ones, he notes. His adds his group has had some success in animal studies using two molecules, laminin and collagen.

"The idea of replacing genes is a very powerful one," Hajjar says. It offers real hope for "an aging population at a very high risk of heart failure." More than 2 million Americans are estimated to have heart failure, and it's responsible for almost 40,000 deaths a year.

There will be "a lot of bumps in the road," Hajjar says. But, he adds, "we are on course to start planning for human trials in the next couple of years."

Further down the road, gene therapy that induces new blood vessel growth may be used to treat ischemic heart disease, in which arteries become clogged, he adds.

More information

You can learn more about integrins from Scientific American. The American Heart Association has more on heart failure.

SOURCES: Roger Hajjar, associate professor, medicine, Harvard Medical School, and researcher, Cardiovascular Research Center, Massachusetts General Hospital, both in Boston; March 4, 2003, Circulation

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