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Donor Lung Supply for Transplant Could Double With Gene Therapy

By Nicole Ostrow

Oct. 28 (Bloomberg) -- Lungs too damaged for use in transplant operations may be salvageable through a gene-based technique, doubling or tripling the supply of organs, said the Canadian author of a report on the method.

The flawed lungs could be removed from donors’ bodies after death and repaired using the gene IL-10, which lowers inflammation, said Shaf Keshavjee, the senior scientist for a study reported today in the journal Science Translational Medicine. Pigs that received organs given this treatment had improved lung function, and laboratory tests showed that IL-10 may boost the performance of human donor lungs too, according to the research.

Last year, 234 people in the U.S. died while waiting for a lung transplant, according to the Organ Procurement and Transplantation Network, a federal program. Currently, more than 1,800 people in the U.S. are waiting for a lung, according to the network. If the method is proven in human trials, the process may become standard for lung transplants within five years, Keshavjee said.

“Worldwide, only 15 percent of donor lungs are used, because those are the ones that we can judge the function to be suitable for transplantation,” said Keshavjee, a senior scientist at the McEwan Centre for Regenerative Medicine, part of the Toronto-based University Health Network, in a telephone interview on Oct. 27.

“By repairing them out of the body and evaluating them and finding out what is wrong with them and repairing them, we can open the door to using more of the lungs successfully and with better outcomes,” said Keshavjee, who also is a professor and department head at the University of Toronto.

Temperature Control

The majority of potential donor lungs currently can’t be used, as they are damaged or have inflammation, wrote the authors, a team of Canadian and U.S. researchers led by Keshavjee.

The researchers warmed the lungs taken from donor cadavers to normal body temperature to help the organs’ cells repair themselves. The scientists took the common-cold virus, removed its genes, and inserted the cytokine interleukin-10 gene. That enabled the virus to carry the IL-10 genes into lung cells, where they reduced inflammation, according to the study.

The lungs that received the therapy had better blood flow and were more able to take in oxygen and expel carbon dioxide, the study showed.

“It’s as if gene therapy turbocharges each individual cell to manufacture many more proteins in its own IL-10 factory,” Keshavjee said in a statement. “This work opens the door for a variety of therapies that could potentially be applied to repair various injuries in other donor organs to improve the safety and outcomes of transplants.”

Avoiding Rejection

The gene is also able to turn down the recipient’s immune system, which otherwise can reject transplanted organs, Keshavjee said.

Human trials -- in which doctors would remove a donor lung, repair it, and transplant it into a live recipient -- may begin in the next year or two, Keshavjee said.

The same concept could be applied to kidneys, livers and hearts as well, he said.

The study reported today was supported by grants from the Canadian Institutes of Health Research and the U.S. National Institutes of Health. Science Translational Medicine, which released its first issue on Oct. 7, is published by the nonprofit Association for the Advancement of Science, based in Washington.

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To contact the reporter on this story: Nicole Ostrow in New York at nostrow1@bloomberg.net.

Last Updated: October 28, 2009 14:00 EDT

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