The US Food and Drug Administration (FDA) has given two biotechnology companies approval for clinical trials to transplant organs from genetically-modified pigs into patients with kidney failure, an experimental but potentially ground-breaking innovation for thousands of Americans on the waiting list for organ transplants.
United Therapeutics said this week that its trial with six patients who have end-stage renal disease will begin around the middle of this year. The trial could expand to 50 people who are unable to receive a donor kidney for medical reasons, or who are on the waiting list but are unlikely to receive one within five years.
Another company, eGenesis, received FDA approval in December for a kidney transplant study on three patients, with the option to expand.
“We are entering a transformative era in organ transplantation,” eGenesis chief executive Mike Curtis told The Washington Post.
Advances in the field of xenotransplantation – transplanting an organ from one species to another – have been gathering pace, as scientists develop gene-editing techniques that make organs less prone to rejection.
Until now, such transplants have been approved under the FDA’s compassionate-use programme, which allows the use of investigational medical products outside clinical trials only when patients are critically ill and running out of options.
Some medical experts have raised ethical and health concerns around such transplants, including the risk of infection from animal-specific diseases that spread among humans, and how to help patients effectively weigh the unknown risks.
Participants in the United Therapeutics trial must be between 55 and 70-years-old and have been on dialysis for at least six months. Patients will be monitored for at least 12 weeks after surgery, and an independent review undertaken before a decision is made on expanding the study.
The idea of using pig organs in humans is not new. One of the first recorded instances was in 1838, when a doctor transplanted a pig cornea into a human in an unsuccessful attempt to fix their eyesight. Pigs are more widely available than some primates, and their organs are more similar to humans, say medical experts.
An Alabama woman last month became the longest-living recipient of a pig organ transplant. In November, Towana Looney (53) received a pig’s kidney with 10 gene edits designed to reduce the risk of organ rejection.
The first recipient, Richard Slayman (62) lived for 52 days after the procedure last year. Lisa Pisano (54) received a pig’s kidney and a heart pump on different days in April last year. She survived 86 days, though the gradually failing kidney had to be removed after 47 days.
The pig used in Looney’s transplant, developed by a subsidiary of United Therapeutics, had changes to its genetic code including the removal of three immunogenic antigens, molecules that can trigger an immune response.
“Our goal is to increase the availability of transplantable organs to offer a therapeutic alternative to a lifetime on dialysis,” Leigh Peterson, executive vice-president of product development at United Therapeutics, said this week.
Longest survivor
Currently, Tooney is thriving and full of energy with her new kidney for 61 days and counting.
She told The Associated Press that she has “a new take on life”.
Her vibrant recovery is a morale boost in the quest to make animal-to-human transplants a reality. Only four other Americans have received hugely experimental transplants of gene-edited pig organs, two hearts and two kidneys, and none lived more than two months.
“If you saw her on the street, you would have no idea she’s the only person in the world walking around with a pig organ inside her that’s functioning,” said Dr Robert Montgomery of NYU Langone Health, who led Looney’s transplant.
Montgomery called Looney’s kidney function “absolutely normal”. Doctors hope she can leave New York – where she’s temporarily living for post-transplant check-ups – for her home in about another month.
“We’re quite optimistic that this is going to continue to work and work well for… a significant period of time,” he said.
How Looney fares is “very precious experience”, said Dr Tatsuo Kawai of Massachusetts General Hospital, who led the world’s first pig kidney transplant last year and works with eGenesis.
Looney was far healthier than previous patients, Kawai noted, so her progress will help inform next attempts.
Looney donated a kidney to her mother in 1999. Later pregnancy complications caused high blood pressure that damaged her remaining kidney, which eventually failed, something incredibly rare among living donors.
She spent eight years on dialysis before doctors concluded she’d probably never get a donated organ – she’d developed super-high levels of antibodies abnormally primed to attack another human kidney.
So Looney sought out the pig experiment. No one knew how it would work in someone “highly sensitised” with those overactive antibodies.
Discharged just 11 days after the 25 November surgery, Montgomery’s team has closely tracked her recovery through blood tests and other measurements.
About three weeks after the transplant, they caught subtle signs that rejection was beginning – signs they’d learned to look for, thanks to a 2023 experiment when a pig kidney worked for 61 days inside a deceased man whose body was donated for research.
Montgomery said they successfully treated Looney and there’s been no sign of rejection since.
There’s no way to predict how long Looney’s new kidney will work but if it were to fail she could receive dialysis again.
“The truth is we don’t really know what the next hurdles are because this is the first time we’ve got this far,” Montgomery said. “We’ll have to continue to really keep a close eye on her.
See more from MedicalBrief archives:
Second person to receive transplanted pig kidney dies
Pig kidney removed from transplant patient after complications