A group of researchers at the University Health Network of Toronto led by Dr. Shaf Keshavjee, developed a novel gene therapy technique that repaired donated lungs deemed too damaged to transplant. The group’s findings, “Functional Repair of Human Donor Lungs by IL-10 Gene Therapy” were published in the October 28, 2009 edition of the journal Science Translational Medicine. Their simple and effective technique could significantly increase the number of available lungs for people desperately in need.
As it stands, only about 15 percent of lungs donated are usable for transplant. Because doctors injure delicate airways as they try to keep donors alive, or the brain death of the donors causes further damage through massive inflammation of the lung tissue. Lungs that make it to transplantation are still vulnerable to inflammation during the first 72 hours after surgery. Overall, only about 40% of lung transplant recipients survive five years after receiving their new lungs.
The research conducted by the University Health Network’s team focused on saving donated lungs that would otherwise be discarded and, eventually, to improve patient outcomes after transplantation. The most important component of their study is the interleukin-10 gene, IL-10. Among IL-10’s many roles is inhibiting the immune response to infection or foreign materials, like transplanted organs. The research strategy consisted of two parts. The first preserved lungs at normal body temperature in a protective dome called the Toronto XVIVO Lung Perfusion System. The dome continuously pumps oxygen devoid of blood, proteins, and nutrients into the injured lungs to mimic normal body conditions. This made it possible for the injured cells to regenerate themselves. In the second part, researchers injected an adenovirus vector, a common cold virus, along with the IL-10 gene through the windpipe into the lungs. After testing the technique with lungs from pigs and then human donors, the team concluded that the gene therapy significantly improved the ability of the lungs to take in oxygen as well as expel carbon dioxide. The therapy improved blood flow throughout the lungs and lasted for up to 30 days. None of the tested lungs were transplanted into patients; however, future plans include starting clinical trials on humans and testing whether this therapy could protect against post-transplant inflammation.