A genetically modified pig kidney transplanted into a brain-dead person has worked for 32 days and counting, advancing efforts to use animals to ease perennial shortages for humans.
Dr. Robert Montgomery and colleagues at NYU Langone Health in New York City transplanted the pig kidney into 57-year-old Maurice Miller on July 14. The results, which haven’t been published, might provide researchers with data to support clinical trials testing animal-to-human transplants.
NYU Langone researchers had previously studied pig hearts and kidneys in humans for up to 72 hours. The shorter period allowed them to see whether the human immune system would immediately reject the pig organs. Transplants of pig organs into baboons had shown another risky period around 14 to 30 days after the procedure.
Extending the duration of studies in brain-dead humans to 30 days and beyond provides new insights, including whether immunosuppressive drugs used in standard kidney transplants can help prevent rejection of pig organs, Montgomery said.
Studying pig-organ transplants for longer periods requires keeping brain-dead people on ventilators, raising ethical and scientific questions. For instance, extending the length of studies delays burial and closure for families. Brain death is defined in the U.S. as the irreversible cessation of brain function, even if heart and lung activity can be maintained with machines.
Miller’s family and a research-oversight committee at NYU Langone agreed to extend the experiment for another 30 days, until mid-September.
To make pig organs more suitable for human transplantation, scientists edit pig DNA. The pig that Montgomery’s team used had one edit, to the gene that produces a sugar molecule on the surface of pig cells that can trigger the human immune system to attack pig organs. Other groups are studying pig kidneys with more gene edits.
“We think less is more,” said Montgomery, chair of the department of surgery and director of the NYU Langone Transplant Institute.
More than 100,000 people in the U.S. are waiting for organs, according to the United Network for Organ Sharing, a nonprofit that helps allocate them. More than 6,000 people die waiting every year.
The system relies on people registering to serve as organ donors. Scientists have spent decades trying to improve transplants among species, or xenotransplantation, as an alternative. Chimpanzees and baboons were early candidates because nonhuman primates are the closest genetic relatives to people. But scientists in recent years have focused on pigs, whose organs are similar in size and function to those of humans. Pigs also produce large litters and are thought less likely than chimpanzees and baboons to transmit viruses to people.
Doctors at NYU Langone and the University of Alabama at Birmingham are among those to seek guidance from the Food and Drug Administration on how to begin clinical trials. Researchers haven’t received FDA clearance. The FDA has asked for additional evidence from pig-organ transplants in baboons before clearing trials in people, researchers said.
The FDA said data from experiments with brain-dead people are difficult to interpret. The cause of death or lifesaving interventions before brain-death can affect outcomes, a spokeswoman said. “The FDA recognizes that the use of xenotransplantation products show great promise, but there are also potential risks,” she said.
Even results from a two-month study in brain-dead people might not be enough to know the procedure is safe, said Dr. Joe Tector, professor of surgery and director of xenotransplant research at Miami Transplant Institute. Tector also started a company making gene-edited pigs for transplants.
“If you get a pig kidney transplant, how long do you want it to last? More than a few months,” he said. “Every inch forward is a battle.”
Doctors at the University of Maryland Medical Center last January transplanted a genetically modified pig heart into David Bennett, a critically ill 57-year-old from Hagerstown, Md. He died two months later. The FDA granted his doctors emergency authorization to perform the surgery.
About 20 days after Bennett’s surgery, the heart he received was found to harbor a pig virus. Researchers have been studying the role that the pig virus might have played in Bennett’s death. The researchers reported in The Lancet earlier this year that the virus might have contributed to the transplant’s failure. Improved testing has been developed to detect viruses in pig organs used in future transplants, the researchers reported.
WHY SCIENTISTS ARE TURNING TO PIGS FOR ORGAN TRANSPLANTS
Human donor organs are in short supply for life-saving transplants. Pig organs have emerged as a potential alternative, in part because pigs are easy to breed and their organs are similar in size to those of humans. And scientists are now able to edit pig genes in ways that make the organs more suitable for transplantation into people.
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