Damaged lungs fixed for transplants
New gene therapy helps patch them
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 inside a see-through life-support dome in the laboratory. But the study published yesterday 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 of the University of Louisville, who wasn’t involved in the new project.
“It’s a long way from prime time,’’ cautioned Bousamra, lung transplant chief at Jewish Hospital in Louisville, Ky. But, he said, “This approach has the potential to change the way we do things.’’
Only about 15 percent of the lungs now provided from otherwise good organ donors are usable for transplant.
The problem often is not 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. And 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 new research, from Toronto’s University Health Network, aims first to save donated lungs that otherwise would be discarded - and if that works, it might help fend off post-transplant damage, too.
The key: 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. But when lungs are donated, they’re quickly put on ice to stop tissue deterioration, and 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. His team created a protective dome to house the lungs, where a solution of oxygen and nutrients is pumped into them, mimicking the body but minus the blood.
Second, insert a gene into those lungs that will quickly produce high levels of IL-10 and reverse the inflammation.
His team reports success in yesterday’s journal Science Translational Medicine. They stuck the IL-10 gene into an adenovirus, from the family of cold viruses, so it would be taken up by lung cells, and snaked the virus inside the airways of the dome-preserved lung.