WASHINGTON — Looking for a way to reduce damage from heart attack and stroke, researchers designed a new combination gene that switches on when oxygen is reduced, triggering a defense mechanism that protects the threatened tissue.
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If it works in humans, the therapy, given in advance to at-risk patients, might provide extra time to get treatment before major damage is done.
In heart attack and stroke, blood supplies to the heart or brain are blocked, resulting in a lack of oxygen that is the major cause of severe injury or death.
“The biggest unmet need is a window of time” to get treatment, said Victor J. Dzau, chancellor of health affairs at Duke University. “While drugs that can protect heart muscle are available, most patients barely make it to the hospital in time to take advantage of them.”
The new therapy may provide that time by protecting tissues from damage, said Dzau, who led the study at Brigham and Women’s Hospital in Boston before moving to Duke in July.
The findings, based on work in rats, are reported in this week’s issue of Proceedings of the National Academy of Sciences.
Dzau said the next step is to try the therapy in larger animals such as pigs and, if all goes well, studies in people could occur in a year or two.
Combination of two genes
The therapy would be for people who have already had a heart attack or have some other high risk factor for having another one, he noted.
Someone who has a high risk of a heart attack in six months to a year would be given the combination gene, which could then activate when needed.
For the therapy, the researchers combined two genes — one that can detect oxygen deficiency and a second one, called heme-oxygenase 1, that protects tissues from damage when they do not get enough oxygen. Then they used a harmless virus to deliver the combination gene to the muscle, liver and hearts of three rats.
Five weeks later, the researchers used tourniquets or clamps to cut off blood. The affected tissues reacted by activating the protective gene, and damage was dramatically reduced compared with rats that did not get the combination gene therapy, Dzau reported.
John Fakunding, program director for heart research at the National Heart, Lung and Blood Institute, called the work “a unique and novel idea, if it can be translated into the clinic. I think it could have a potential for certain patients.”
The problem with trying to protect the heart is not knowing when a heart attack may occur, he observed. With this therapy, someone at high risk of a heart attack could be treated in advance.
The research was funded by the National Institutes of Health, the Edna Mandel Foundation and the Canadian Institutes of Health Research.
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