Gene-edited pig kidney functions well in human body for more than a month
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Key takeaways:
- A gene-edited pig kidney transplanted into a brain-dead man’s body is functioning well more than 4 weeks later.
- The kidney required fewer genetic modifications for successful transplant than previous organs.
A genetically engineered pig kidney is functioning well more than a month after being transplanted into the body of a man declared dead by neurologic criteria, doctors announced.
The xenotransplantation was the fifth performed by physicians at the NYU Langone Transplant Institute, who previously performed the world’s first transplant of a genetically modified pig kidney into a human body in September 2021, followed by a similar procedure 2 months later.
Surgeons at the institute have also performed two transplants of genetically modified pig hearts into recently deceased humans.
Although most xenotransplants have involved donated bodies, last year a surgical team at the University of Maryland Medical Center transplanted a genetically modified pig heart into a 57-year-old man who survived for 2 months after the procedure.
Previous pig organ transplants have had up to 10 genetic modifications for compatibility with the human immune system and to prevent rejection of the organ, according to an NYU Langone Health press release. In the new procedure, however, the kidney had just a single gene modification.
Surgeons removed both of the man’s kidneys to be sure that only the pig kidney was sustaining kidney function in the body. The kidney began producing urine immediately after the procedure and has not been rejected, NYU Langone said.
“We’ve now gathered more evidence to show that, at least in kidneys, just eliminating the gene that triggers a hyperacute rejection may be enough, along with clinically approved immunosuppressive drugs to successfully manage the transplant in a human for optimal performance — potentially in the long term,” Robert Montgomery, MD, DPhil, chair of the NYU Langone surgical department and director of the institute, said in the release.
The procedure, led by Montgomery, was performed on July 14 and involved a 57-year-old man whose family elected to donate his body because his organs and tissues were unusable for transplant, NYU Langone said. The man was kept alive with a beating heart and on ventilator support.
The kidney and thymus gland used for the procedure were from a GalSafe pig, which are engineered using CRISPR-Cas9 to delete the gene that encodes for alpha-gal, a sugar molecule found in mammals that has been identified as the cause of rapid transplant rejection. The pigs have also been approved by the FDA as food for people with alpha-gal syndrome, a potentially life-threatening allergic rection primarily associated with tick bites.
According to the release, ICU staff monitored the organ, taking weekly biopsies and measuring creatine levels, which were in the “optimal range” during the 4 1/2 weeks after transplant.
As of Aug. 16, the kidney was functioning well for 32 days — the longest a gene-edited pig kidney has functioned in a human, according to NYU Langone.
Xenotransplantation is seen as a potential solution to the ongoing organ shortage crisis and an emerging issue in transplant infectious diseases, according to experts, because of the associated risk for infection with a range of pathogens, including porcine cytomegalovirus, which can affect organ performance and potentially trigger organ failure.
According to NYU Langone, the surgical team used standard immunosuppressive medications for the recent procedure and screened the donor pig for porcine CMV. They continue to test for both porcine CMV and seven other viruses, including porcine endogenous retrovirus.
With more than 104,000 people awaiting organ transplants in the United States, and about 88,000 waiting for kidneys, Montgomery said xenotransplantation “is a viable way” to overcome the shortage.
“We think using a pig already deemed safe by the FDA, in combination with what we have found in our xenotransplantation research so far, gets us closer to the clinical trial phase,” Montgomery said. “We know this has the potential to save thousands of lives, but we want to ensure the utmost safety and care as we move forward.
References:
- HRSA. Organ donation statistics. https://www.organdonor.gov/learn/organ-donation-statistics. Accessed Aug. 18, 2023.
- Pig kidney xenotransplantation performing optimally after 32 days in human body. https://nyulangone.org/news/pig-kidney-xenotransplantation-performing-optimally-after-32-days-human-body. Accessed August 16, 2023