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Advances in lung transplantation powered by genomics

April 1, 2015

Genomics-based diagnostics are revolutionizing medicine, including in unexpected places like organ transplantation.

Diagnostic toolboxes are being revolutionized by the impact of so-called “next-generation sequencing” because of the speed, low cost and breadth of information provided. The fields of prenatal diagnosis, rare disease diagnosis and cancer treatment are leaders in adoption of this technology. Not as well-known is the potential impact on organ transplantation.

Transplant surgeon Dr. Shaf Keshavjee and team at the University Health Network recently discovered a set of genomic markers that better identify which lungs are suitable for transplantation. With recent funding from Genome Canada and in partnership with the U.S. biotechnology firm Lung Biotechnology Inc. (a subsidiary of United Therapeutics Inc., a large publicly-traded biotechnology company), these markers are to be developed into a rapid diagnostic product to be used worldwide.

Dr. Shaf Keshavjee and his team have already made headlines with their work to improve the success of lung transplantation. Now the international standard, they developed a method of perfusing lungs with a lung preservation solution in a warmed chamber after removal from the donor. This has been shown to reduce the incidence of primary graft dysfunction after transplantation by fifty percent.

This method, called “ex-vivo lung perfusion” (EVLP) also opens a brief time window in which lungs can be better assessed before transplantation. This is important because over 85% of donor lungs are rejected for transplant due to quality concerns. Current assessment methods are based on a set of physiological markers and may be overly strict in order to avoid problems in patients after transplantation. The importance of the new genomic markers is that they will allow a more precise determination of donor lung health, and Dr. Keshavjee predicts that using these as diagnostic tests will more than double the percentage of lungs deemed usable. The availability of healthy donor lungs is the rate-limiting step for those waiting for a new lung – in 2013, 314 Canadians were listed on the waiting list, whereas only 247 lung transplants were reported in Canada in the same period.

Dr. Keshavjee is also using the genomic markers to guide the development of gene therapy-based treatments of donor lungs while under EVLP. His objective is to improve the health of donor lungs and circumvent processes that lead to problems after transplantation. This will help make the best use of the existing donor pool as well as improve outcomes after transplantation.

By: Kathryn Deuchars, Director, Ontario Personalized Medicine Network