Who wants a pig organ? Patients sick and tired of waiting years for a transplant
LOUISVILLE, Ky. — The calls and emails started coming in NYU Langone Health And Massachusetts General Hospital soon after, doctors began experimenting with pig organs in humans.
People who feared they would never get a scarce human transplant wondered: When could we do that? take a pig kidney?
Alex Berrios of Louisville, Kentucky, needs a second transplant, but finding another human match is proving impossible. That is why he keeps a close eye on whether there is a chance of research into pig kidneys.
“Maybe it won’t work, and I have to be okay with that,” Berrios said. “I think it’s worth it.”
Now two US companies aim to begin the world’s first clinical trials in xenotransplantation in 2025 – using pig kidneys or hearts to try to save human lives. Potential volunteers are eager to see if they qualify as researchers fine-tuning how best to test whether the humanized pig organs they’ve designed might actually work.
Anticipation is growing with news that an Alabama woman was doing well after a pig kidney transplant at NYU in late November. Towana Looney is the fifth American to receive a gene-edited pig organ, all so far a stopgap experiment for people without options.
None of the previous recipients – two given pig hearts And two kidneys – survived more than two months but that has not stopped researchers from looking for an alternative to the acute shortage of transplantable organs.
“We must have the courage to continue,” says transplant surgeon Dr. Bartley Griffith.
In 2022, Griffith was struggling to figure out how to ask a dying patient if he would consider having the world’s first transplant of a genetically modified pig heart.
“I was so scared to mention the word pig heart,” Griffith said. He was surprised that patient David Bennett responded with a joke about grunting and clarified whether that was the case last desperate attempt failed that “maybe you will learn something for others like me.”
Fast forward to late 2023, when at a National Kidney Foundation meeting with FDA officials and pig developers, patients described lives so miserable on dialysis that they, too, would risk an animal organ.
“Why not try? That was really what we took back,” said Mike Curtis, CEO of eGenesis, one of the organ development companies. “It was like we really almost had an obligation to try.”
“The patients pushed us to keep going,” agreed Dr. Tatsuo Kawai, a Mass General surgeon who was hesitant to even broach the idea — but last March, four months after that meeting, a longtime patient provided the first gene-modified treatment. pig kidney.
In Palm Springs, California, Carl McNew emailed NYU with questions about volunteering while he was still in reasonable health.
McNew donated a kidney to his husband in 2015, but later his remaining kidney began to deteriorate, which is very rare among living donors. Medications and intermittent dialysis help, but McNew knows he will eventually need a transplant.
“There’s just something about being part of something like that, it’s so cutting edge,” says McNew, who saw news of NYU’s xenotransplantation research in 2023 and emailed his interest.
For Berrios of Louisville, donor scarcity isn’t the only obstacle. Born with a single kidney that failed in his late 20s, a living donor transplant restored his health for 13 years. But in 2020 it failed and he has since developed antibodies that would destroy another human kidney, which doctors call “highly sensitive.”
Every Monday, Wednesday and Friday, Berrios quietly sneaks out of his house before dawn to spend nearly four hours strapped to a dialysis machine. Going through the grueling treatments at 5am is the only way the father of two can both stay alive and hold down a full-time job.
But dialysis does not completely replace kidney function; people are slowly getting sicker. So even as Berrios tried an experimental therapy to address his problematic antibodies, he told NYU he was interested in a pig kidney.
FDA rules require that pig organs be extensively tested in monkeys and baboons before humans. And while researchers have extended the survival of these primates to a year and sometimes even longer, they were desperate for human experiences. After all, pig organs have been genetically altered to be more human, not more baboon-like.
At NYU and the University of Alabama at Birminghamsurgeons first tested pig organs in bodies of recently passed away, donated for scientific research.
And patients who have received pig organs have so far been “compassionate use” transplants, experiments that the FDA allows in select emergency situations for people who have no other options.
Although the first four did not survive long, partly due to complications from other diseases, these experiments proved that pig organs could work for at least a while and offered other lessons. For example, the discovery of a hidden pig virus in the first heart transplant led to better testing for that risk.
Only rigorous studies comparing similarly ill patients will provide a clearer picture of the potential of pig organs – perhaps Looney’s. Despite eight years of dialysis, she was not nearly as sick as previous xenotransplant recipients, but she could not find a matching donor. Like Berrios, she had a highly sensitized immune response.
Looney could be “kind of a litmus test” for trial candidates, said NYU’s Montgomery, who led her transplant with her original surgeon in Alabama, Dr. Jayme Locke. “She got the transplant at just the right time,” before the dialysis did too much damage.
Scientists have tried animal-to-human transplants for years without success, but now they can edit pig genes, in an effort to bridge the gap between species enough to prevent the human immune system from immediately attacking the foreign tissue. Yet no one knows the best gene combination.
Revivicor, a subsidiary of United Therapeutics, produces kidneys and hearts with 10 gene edits, knocking out pig genes that cause hyperrejection and excessive organ growth and adding some human genes to improve compatibility. Maryland used hearts with 10 gene edits in its two xenotransplants. Looney also received a kidney with ten gene edits, based on Locke’s research while she worked in Alabama.
Although Montgomery is happy with Looney’s progress, he has done most of his work with Revivicor pigs with only one gene editduring a xenotransplantation last April and during research with the deceased.
“Our feeling is, you know, less is more,” Montgomery said, noting that it is easier to mass produce pigs with fewer gene changes. Looney’s transplant offers a chance to compare “how much of a difference these additional gene edits really make.”
In Boston, eGenesis has another approach: no fewer than 69 gene edits. In addition to 10 genetic changes to improve human compatibility, genes associated with certain pig viruses are also inactivated.
Researchers are feeling pressure to show whether pig organs can keep people alive much longer than a few months, says Curtis of eGenesis. If not, the question will be: do we have the right gene edits?
The balance is that participants are sick enough to qualify, but not so sick that they don’t have a chance.
“There are a huge number of patients who would be very willing to do this,” says Dr. Silke Niederhaus of the University of Maryland, who is not involved in xenotransplant research but is keeping a close eye on it.
Niederhaus became a kidney transplant surgeon because someone saved her life around the age of 12. That kidney lasted three decades. When it failed, it took five years to find another. So she understands the appeal of pig research and urges people to learn their chances of receiving a human kidney before volunteering.
If they’re younger and healthier or have a living donor, “I would probably say go with what’s known and what’s proven,” Niederhaus said. But if they’re older and dialysis starts to fail, “it might be worth taking the risk.”
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AP video journalist Shelby Lum contributed to this story.
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