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Gene therapy mends damaged lungs for transplant

2 November 2009
Appeared in BioNews 532

Donor lungs damaged before transplantation can be repaired using a gene therapy technique developed by a team of scientists in Canada. This may increase the supply of functional lungs for transplant patients, by using organs that are currently discarded.

Shortage of donor organs is a worldwide problem. Around 10,000 people are waiting for transplants in the UK alone, a figure that is rising by eight per cent every year. The shortage of organs required means that last year, while 143 lung transplant operations took place, 216 patients were on the waiting list for a lung.

The shortage is in part due to damage that occurs to the lung during death, either from inflammation after brain-death or in intensive care complications, which deems around 80 per cent of donated lungs unsuitable for transplant. Donor lungs are also chilled on ice, which destroys an important immune molecule called interleukin-10 (IL-10). This allows substantial damage to occur to the lung before transplantation and also increases the risk of rejection after transplantation due to inflammation.

Dr Shaf Keshavjee, Director of the Lung Transplant Programme of the University Health Network, led the group of scientists with his colleague Dr Marcelo Cypel, transplant surgical fellow at the Toronto General Hospital, who is lead author on the paper. They created a two-tiered approach to combat the damage endured by donor lungs, and tested it on both human and pig lungs. Firstly, the lungs were incubated at body temperature in a specially designed protective dome, and a bloodless solution of oxygen, proteins and nutrients pumped through them, mimicking physiological conditions. Then, using an engineered adenovirus vector from the common cold virus, gene therapy was used to insert IL-10 into the lungs.

When compared to control lungs that were incubated with the solution but not subjected to gene therapy, which did not deteriorate and remained stable, the doubly treated lungs exhibited improved function, measured by blood flow and their ability to take in oxygen and use up carbon dioxide. IL-10 levels were increased and remained so for 30 days in these lungs.

The team transplanted some of the repaired pig lungs into pigs, and found that they were functioning significantly better four hours after transplant than lungs that were not subjected to gene therapy. The next step will be to use the technique in clinical trials involving human patients. The lungs would be offered to critically ill, consenting patients if no other lungs were available.

Dr Keshavjee explained that IL-10 'decreases the inflammatory potential of cells injured before and during the transplant process. It also has the capacity to turn down the recipient's immune system which rejects the transplanted organ'. Several questions remain, in particular concerned with the safety of using an adenovirus vector. The researchers, however, say that helping the organ to function better at the time of transplantation should lead to more predictable, safer outcomes in terms of rejection. There is hope that the number of donor organs available for lung transplants could be doubled with this technique.

SOURCES & REFERENCES
Donor lungs could be 'refurbished' with IL-10 gene therapy
The Times |  29 October 2009
Gene therapy may boost success of lung transplants
LA Times |  29 October 2009
Gene Therapy Repairs Injured Human Donor Lungs For The First Time
Science Daily |  28 October 2009
Scientists patch damaged lungs for transplanting
AP |  29 October 2009
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