This photo shows what the 10-gene edited pig kidney looked like after reperfusion. The probe is a Doppler that documented excellent signals throughout the kidney. Credit: Jeff Myers, UAB
Key points:
- The team behind extensive xenotransplant kidney research has developed an optical immunosuppression regiment that relies solely on already FDA-approved medications.
- The regiment involves combining common immune-suppressing drugs with a complement inhibitor.
- With the medications already approved, the team hopes it will lead to quicker approval of a Phase I clinical trial in living humans.
The pioneering scientists behind xenotransplant kidney research have made another critical advancement—using already FDA-approved drugs, they have discovered the optimal immunosuppression regimen for pig-to-human kidney transplants.
“It’s a major departure from what’s been tried before in most non-human primate experiments and living human heart transplants, but it’s with a treatment regimen transplant doctors work with every day,” said Jayme Locke, professor of surgery at University of Alabama at Birmingham and lead author of the new paper.
The regimen involves combining common immune-suppressing drugs with a complement inhibitor, all of which have already been approved by the FDA as transplant medication.
The study, published in the Journal of Clinical Investigation, examines the case series of three decedent model xenotransplants. Locke and team used standard immunosuppression in the first decedent model, but they did not use a complement inhibitor. While the biopsies of the pig kidneys were histologically normal in the first model after being transplanted on the first day, they began to show some signs of rejection the day after transplant.
With the second and third decedent model studies, researchers used standard immunosuppression and added a complement inhibitor. The complement inhibitor prevented the immune system from forming a membrane attack complex, a microscopic “battering ram” that breaks through a cell’s defenses, ultimately causing organ failure. Instead, when the complement inhibitor was used, the transplanted pig kidneys did not reject and were able to provide life-sustaining function.
“The membrane attack complex essentially sets up like a little drill on the surface of a cell and it drills holes in the cell,” Locke said. “If you drill holes in the cell, it weakens and it dies. If you kill enough cells, then the tissue dies. If you kill enough tissue, then the organ dies. The complement inhibitor prevents the formation of this drill on the surface of the cell. It’s like creating a force shield around the kidney.”
The study findings advance the science and promise of xenotransplantation as a therapy to potentially cure end-stage kidney disease, as well as address the worldwide kidney organ shortage crisis. Currently, more than 800,000 people in the United States are living with kidney failure and 90,000 people are awaiting a kidney transplant.
“This is another critical piece that I hope will soon lead to FDA clearance for a Phase I clinical trial in living humans,” said Locke.