For patients with end-stage organ disease, an organ transplant is often the best treatment. However, transplant patients have to take powerful medications to prevent their immune system from rejecting a donor organ, and these medications can have severe side effects. Even with these medications, 1 out of every 4 transplanted organs are still attacked by the patient’s immune system. Division of Transplantation Assistant Professor David Al-Adra, MD, PhD is interested in finding ways to alter donor organs before they are transplanted to decrease the chance of rejection. This is the focus of a new two-year, $100,000 grant that Al-Adra recently received from the American Society of Transplant Surgeons.
“There are two key proteins in organ tissue that are known to have properties that can quiet the immune system. Our collaborator, Dr. Jacques Galipeau, recently fused these two proteins together,” explained Al-Adra. “If we can find a way to get a donor organ to express these proteins before the organ is transplanted, our hope is that the fused protein will help keep the patient’s immune system in check after the transplant surgery.”
Working with Dr. Galipeau, who is a Professor in the UW Department of Medicine, the research team will be using a liver storage technique called normothermic ex vivo liver perfusion (NEVLP). This technique allows a transplant team to keep a donor liver warm and functioning by continuously pumping blood through it before the transplant surgery – and for Al-Adra’s team, it provides the perfect opportunity to deliver the fused protein to the donor organ. Testing this theory in a rat model of liver transplantation, their first task will be to get the donor rat liver to express the fused protein during NEVLP. Once the donor organ is expressing the fused protein on its own, they will transplant the liver into another rat and monitor the liver for signs of rejection
“If we’re successful in a rat model, we’ll apply for future grants that can test the safety and effectiveness of the fused protein in larger animal models,” said Al-Adra. “My goal is that we can develop a new strategy that will reduce the risk of organ rejection and reduce the need for harmful anti-rejection medications, which would help improve outcomes for the 43,000 patients who receive a transplant each year.”