February 22, 2024

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Breakthrough in Safe Pig-to-Human Organ Transplants: Optimal Immune Suppression Identified

Breakthrough in Safe Pig-to-Human Organ Transplants: Optimal Immune Suppression Identified



Breakthrough in Safe Pig-to-Human Organ Transplants: Optimal Immune Suppression Identified

In a groundbreaking step towards safer pig organ transplants into humans, recent research identifies the best immune suppression strategy.

The findings, published in the American Journal of Transplantation in April 2022 by the team led by Jayme Locke from the University of Alabama at Birmingham, showcase successful transplantation of genetically edited pig kidneys into a brain-dead human.

The pig kidneys not only filtered blood and produced urine but, crucially, did not trigger immediate rejection. These pig kidneys maintained functionality until the conclusion of the study, lasting 77 hours post-transplant.

In August 2023, Locke’s team reported in JAMA Surgery on the performance of genetically edited pig kidneys transplanted into brain-dead humans. The experiment spanned a week, during which the pig kidneys operated effectively, providing vital kidney functions for seven days.

On January 25, 2024, Locke’s team achieved further progress, publishing a study titled “C5 inhibition with eculizumab prevents thrombotic microangiopathy in a case series of pig-to-human kidney xenotransplantation” in the Journal of Clinical Investigation.

Breakthrough in Safe Pig-to-Human Organ Transplants: Optimal Immune Suppression Identified

The research highlights that the optimal immune suppression strategy for pig kidney-to-human transplants involves using FDA-approved organ transplant drugs (tacrolimus) combined with another FDA-approved complement inhibitor (eculizumab). This development is a significant stride towards addressing the global organ transplant shortage crisis through pig organ xenotransplants.

The study establishes an ideal immune suppression strategy for pig kidney-to-human transplants, effectively managing the initial immune response to transplanted pig kidneys, according to the research team.

In this latest study, Locke’s team explored three pig kidney xenotransplant cases in brain-dead patients that they had previously conducted. In the first case, standard immune suppressants were used without complement inhibitors. The genetically edited pig kidney initially functioned normally but exhibited rejection signs from the second day onwards.

In the second and third cases, the team used standard immune suppressants (tacrolimus) alongside a complement inhibitor (eculizumab), an FDA-approved drug for treating a rare kidney disease called atypical hemolytic uremic syndrome (aHUS). Complement inhibitors prevent the immune system from forming membrane attack complexes (MAC) that breach cell defenses, ultimately leading to organ failure.

With the combination of complement inhibitors, the transplanted pig kidneys showed no signs of rejection and could sustain life functions. Professor Jayme Locke explained that membrane attack complexes essentially act like small drills on the cell surface, causing cell weakening and death. Sufficient cell death results in tissue death, and enough tissue death leads to organ failure. Complement inhibitors prevent cell death caused by membrane attack complexes, creating a protective shield around the kidneys.

The pig kidneys used in these studies were sourced from Revivicor’s genetically engineered pigs, modified with 10 gene edits, including the insertion of six human genes – two human complement inhibition genes (hDAF and hCD46), two human anticoagulant genes (hTBM and hEPCR), and two human immune-regulating genes (hCD47 and hHO1). Additionally, four pig genes were knocked out to eliminate α-Gal oligosaccharides from pig cells, prevent rejection reactions, and reduce the size of the pigs to control organ size.

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Breakthrough in Safe Pig-to-Human Organ Transplants: Optimal Immune Suppression Identified

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