Two-month study of a transplanted genetically engineered pig kidney into a human gives new hope

USA: NYU Langone Health doctors have completed the longest-documented case of a genetically engineered pig kidney functioning in a human body following 61 days of observation.

The procedure, known as a xenotransplant, which involves the transplant of an animal organ into a human, was performed on July 14, 2023, and led by Robert Montgomery, MD, DPhil, the H. Leon Pachter, MD, Professor and chair of the Department of Surgery and director of the NYU Langone Transplant Institute. The organ was removed on September 13, 2023, from a 58-year-old man who had been on a ventilator, with his family’s consent, after being declared dead by neurologic criteria before the xenotransplant.

“We have learned a great deal throughout these past two months of close observation and analysis, and there is great reason to be hopeful for the future,” said Dr. Montgomery. “None of this would have been possible without the incredible support we received from the family of our deceased recipient. Thanks to them, we have been able to gain critical insight into xenotransplantation as a hopeful solution to the national organ shortage.”

The study was concluded after reaching its predetermined end date, with the decedent removed from the ventilator and his body returned to the family, as per their wishes.

The procedure was the fifth xenotransplant performed by the Transplant Institute since Dr. Montgomery performed the world’s first genetically modified pig kidney transplant into a human on September 25, 2021. That was followed by a second similar procedure on November 22, 2021. Surgeons at NYU Langone then performed two genetically engineered pig heart transplants in summer 2022.

The kidney used in this procedure was procured from what is known as a GalSafe pig, an animal engineered by Revivicor Inc., a subsidiary of United Therapeutics Corporation. In December 2020, the U.S. Food and Drug Administration (FDA) approved the GalSafe pig as a potential source for human therapeutics, as well as a food source for people with alpha-gal syndrome, a meat allergy caused by a tick bite.

By “knocking out” the single gene that encodes the biomolecule known as alpha-gal-which has been identified as responsible for a rapid antibody-mediated rejection of pig organs by humans-immediate rejection has been avoided in all five xenotransplants at NYU Langone. Additionally, the pig’s thymus gland, which is responsible for educating the immune system, was fused with the pig kidney to stave off novel, delayed immune responses.

While previous genetically engineered pig organ transplants have incorporated up to 10 genetic modifications, this latest study shows that a single-gene knockout pig kidney can perform optimally after two months.

Novel Findings and Next Steps

Tissue collected during the study indicated some novel cellular changes that surgeons had not previously observed, indicating a mild rejection process that required intensifying immunosuppression medication in order to reverse it completely.

The research team will now pour over data collected from the past two months and conduct additional tests to determine cellular and molecular changes that may inform clinicians on how to manage these organs in future studies-and one day in living humans.

In the United States, there are more than 103,000 people on the waiting list for a transplant, with nearly 88,000 of those waiting for a kidney, according to recent federal Organ Procurement and Transplantation Network (OPTN) data. In 2022, about 26,000 people received a kidney transplant. Meanwhile, nearly 808,000 people in the United States have end-stage kidney disease.

“In order to create a sustainable unlimited supply of organs, we need to know how to manage pig organs transplanted into humans,” said Dr. Montgomery. “Testing them in a decedent allows us to optimize the immunosuppression regimen and choice of gene edits without putting a living patient at risk.”

Dr. Montgomery expects to publish more detailed findings in the coming months, while pursuing additional xenotransplantation studies in decedents to make future clinical trials safer.

The procedure, known as a xenotransplant, which involves the transplant of an animal organ into a human, was performed on July 14, 2023, and led by Robert Montgomery, MD, DPhil, the H. Leon Pachter, MD, Professor and chair of the Department of Surgery and director of the NYU Langone Transplant Institute. The organ was removed September 13, 2023, from a 58-year-old man who had been on a ventilator, with his family’s consent, after being declared dead by neurologic criteria before the xenotransplant.

“We have learned a great deal throughout these past two months of close observation and analysis, and there is great reason to be hopeful for the future,” said Dr. Montgomery. “None of this would have been possible without the incredible support we received from the family of our deceased recipient. Thanks to them, we have been able to gain critical insight into xenotransplantation as a hopeful solution to the national organ shortage.”

The study was concluded after reaching its predetermined end date, with the decedent removed from the ventilator and his body returned to the family, as per their wishes.

The procedure was the fifth xenotransplant performed by the Transplant Institute since Dr. Montgomery performed the world’s first genetically modified pig kidney transplant into a human on September 25, 2021. That was followed by a second similar procedure on November 22, 2021. Surgeons at NYU Langone then performed two genetically engineered pig heart transplants in summer 2022.

The kidney used in this procedure was procured from what is known as a GalSafe pig, an animal engineered by Revivicor Inc., a subsidiary of United Therapeutics Corporation. In December 2020, the U.S. Food and Drug Administration (FDA) approved the GalSafe pig as a potential source for human therapeutics, as well as a food source for people with alpha-gal syndrome, a meat allergy caused by a tick bite.

By “knocking out” the single gene that encodes the biomolecule known as alpha-gal—which has been identified as responsible for a rapid antibody-mediated rejection of pig organs by humans—immediate rejection has been avoided in all five xenotransplants at NYU Langone. Additionally, the pig’s thymus gland, which is responsible for educating the immune system, was fused with the pig kidney to stave off novel, delayed immune responses.

While previous genetically engineered pig organ transplants have incorporated up to 10 genetic modifications, this latest study shows that a single-gene knockout pig kidney can perform optimally after two months.

Novel Findings and Next Steps

Tissue collected during the study indicated some novel cellular changes that surgeons had not previously observed, indicating a mild rejection process that required intensifying immunosuppression medication in order to reverse it completely.

The research team will now pour over data collected from the past two months and conduct additional tests to determine cellular and molecular changes that may inform clinicians on how to manage these organs in future studies-and one day in living humans.

In the United States, there are more than 103,000 people on the waiting list for a transplant, with nearly 88,000 of those waiting for a kidney, according to recent federal Organ Procurement and Transplantation Network (OPTN) data. In 2022, about 26,000 people received a kidney transplant. Meanwhile, nearly 808,000 people in the United States have end-stage kidney disease.

“In order to create a sustainable unlimited supply of organs, we need to know how to manage pig organs transplanted into humans,” said Dr. Montgomery. “Testing them in a decedent allows us to optimize the immunosuppression regimen and choice of gene edits without putting a living patient at risk.”

Dr. Montgomery expects to publish more detailed findings in the coming months, while pursuing additional xenotransplantation studies in decedents to make future clinical trials safer.