Posted on December 23, 2013
by Derek Quizon
Lung transplants are exceedingly difficult to pull off. Once a donor dies, doctors typically have between six and eight hours to perform the transplant. Many of the lungs expire before then, said University of Virginia microbiologist Victor Laubach.
“If there’s someone waiting for a lung in Miami but the only lung that matches them is in Seattle, Wash., right now that’s too far away,” Laubach said. “A lot of patients die because they don’t find a suitable donor.”
But Laubach and a team of researchers at the UVa Medical Center believe they can change that with the development of a new drug. The idea is to use the drug, in combination with existing technology, to preserve lungs for up to 24 hours. That means doctors could conceivably get lungs to people on the transplant list in any part of the country.
“If we can implement this … we might ultimately be able to eliminate the lung transplant wait list,” said Laubach, co-principal investigator in a project that has received a $3.3 million grant from the National Institutes of Health.
His partner, Dr. Irving L. Kron, is a little more conservative. But he said the drug, based on an anti-inflammatory medication called Adenosine, could have a wide-ranging impact on the medical field.
“All the surgeries we do are complicated by inflammation,” Kron said. “If this thing is proved safe, I could see it being used far beyond our little field.”
By most estimates, about 15 percent to 20 percent of donor lungs end up being usable. The shelf life on most organs is limited immediately after death, Laubach said, but lungs are especially sensitive to the lack of oxygen and blood flow.
Lungs that have been starved of oxygen and blood for too long can cause reperfusion injury, which is characterized by severe inflammation and tissue damage. If lungs have been outside the body too long, they may simply be discarded because the risk is too great, Laubach said.
The condition is characterized by severe inflammation, which can hinder the function of a patient’s transplanted organ just hours after the procedure. Kron said complications years after surgery may be linked with injuries to lungs early in the transplant process.
“It occurs because of injury that occurs before the lungs are transplanted,” Kron said. “That’s the reason lungs fail in the long run.”
The (potential) solution
Current technology, using a machine called Ex Vivo Lung Perfusion, allows doctors to keep lungs alive for a few hours by pumping oxygen into them. Kron and Laubach said they believe that by using a modified version of Adenosine, they can widen that window, and even reverse some of the damage incurred by lungs after the donor’s body shuts down.
“We’re hoping we can enable these lungs to be stored on ice for up to 24 hours,” Laubach said.
Even if the drug is approved by the Food and Drug Administration — which is several years away —such a transplant would still be a complicated and delicate procedure. After the patient dies, the lungs would be put into the EVLP machine to be preserved. Doctors would pump the drug into the soon-to-be-transplanted lung.
This won’t help lungs that have been severely damaged by chronic disease, Kron said, but it would still widen the range of possible successful donors.
“You could certainly use a lot more lungs than we use now,” he said.
Years in the making
Kron and Laubach have been testing this use of Adenosine in animals for almost 10 years. Typically, Kron said, the drug helps activate anti-inflammatory molecules in the bodies of the pigs receiving the new lungs, which nips the problem in the bud.
“If we can get that receptor activated right at the time the blood starts flowing … in all our animal studies, we can nearly prevent reperfusion injury from occurring,” Laubach said.
Though they’ve successfully secured NIH funding, the team is still working on an application for FDA testing. That could take years of trials and studies, but Laubach said he, Kron and the rest of the team are confident about the drug’s chances.
“The research we’ve been doing is all telling us we’ll likely be successful,” Laubach said.