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Date published: 11/1/2009
BY LAURAN NEERGAARD AP MEDICAL WRITER
WASHINGTON --Call it a genetic patch job for worn lungs: Canadian researchers took donated lungs deemed too damaged to transplant and repaired them with outside-the-body gene therapy.It will take lots more research to see if the fix lasts, to find out if the lungs work as well back inside a body as they do in the laboratory. But the study has lung specialists hopeful they can boost the number of lungs available for people desperately in need. "We've been banging our heads against the wall with respect to lung transplant survival for quite some time," said Dr. Michael Bousamra, lung transplant chief at Jewish Hospital in Louisville, Ky., who wasn't involved in the new project. The approach is "a long way from prime-time," cautioned Bousamra. But, he added, "This approach has the potential to change the way we do things." SAVING MORE LUNGS Only about 15 percent of the lungs now provided from otherwise good organ donors are usable for transplant. The problem often isn't that the lungs were diseased. Rather, the delicate airways were damaged as doctors tried to keep the donor alive. Or, brain death caused massive inflammation that triggered further damage. Lungs that are transplanted are vulnerable to a cascade of inflammation in the first three days post-surgery. In fact, the five-year survival of lung transplant recipients is barely 50 percent, worse than for heart, liver or kidney recipients. The research, from Toronto's University Health Network, aims to save donated lungs that otherwise would be discarded. If that works, it might fend off post-transplant damage, too. FIRST PIGS, THEN HUMANS The key to the new approach: A gene that produces a substance called interleukin-10. Among IL-10's many jobs is tamping down inflammation from the molecules most prone to damage lungs. Donated lungs are quickly put on ice to stop tissue deterioration, and that keeps whatever IL-10 remains from working. So Dr. Shaf Keshavjee, University Health Network's lung transplant chief, devised a two-part fix: First, create a body-temperature chamber that will keep the lungs alive outside the body. Second, insert a gene into those lungs to quickly produce high levels of IL-10 and reverse the inflammation. Using lungs first from a handful of pigs and then from humans--10 donor lungs that had been rejected for transplant--the team found that lungs receiving the gene therapy significantly improved their ability to take in fresh oxygen and get rid of carbon dioxide. The human lungs weren't transplanted into sick patients. That's a much bigger step that Keshavjee hopes to try in an experiment sometime in the next year. But
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