The xenotransplant team at the University of Alabama-Birmingham which was able to successfully preform a transplant of a pig kidney to a brain-dead human patient.
UAB University Relations
The successful transplantation by scientists at University of Alabama-Birmingham into a brain-dead human body paves the way to clinical trials — and hope for thousands of patients suffering kidney disease.
Over 80,000 people are currently on the waitlist to receive a kidney donation, according to the Health Resources and Services Administration, but only around 20,000 kidney donations are performed each year. Patients have to wait on average nearly 4 years to get a kidney, and in the meantime have to suffer from kidney disease and renal failure. Hundreds of others die before a transplant is made available.
The number of patients in need of a transplant will continue to number in the tens of thousands each year if current trends continue. There are about 37 million Americans with some type of chronic kidney disease, and 800,000 are at some stage of kidney failure.
In September 2021, researchers at the University of Alabama-Birmingham (UAB) made a major step towards helping more kidney patients get the organs they need. They did this by successfully performing a kidney transplant from a gene-edited pig into a brain-dead human patient. The transplanted organs were able to successfully perform kidney functions including production of urine and filtering blood. No signs of host rejection were seen for the 77 hours of the peer-reviewed study, which was published Thursday in the American Journal of Transplantation.
“This was truly a team effort. I think we did it the right way. I think it’s important that this has been peer reviewed,” Jayme Locke, head of the Comprehensive Transplant Institute at UAB’s surgery department said in a press briefing. Locke was also the lead surgeon for the procedure. “We were able to critically catch critical components of the pathway that will be necessary to move this into living people, beyond a one-off transplant,” she continued.
The kidneys used in this transplant came from a genetically modified pig developed by Revivicor, a subsidiary of United Therapeutics. This particular line of pigs has 10 key gene edits that are designed to both prevent a human immune system from rejecting the organ, as well as a key edit that constrains the size of the pig kidney to better match a human kidney. The pigs themselves were raised in a pathogen-free facility.
“We know Jim is very proud that his death could potentially bring so much hope to others,” the Parsons family said in a statement.
Courtesy of Parsons family
The recipient of this experimental transplant was a brain-dead patient, Jim Parsons, whose body was kept on life support for the procedure. Though he was a registered organ donor, his organs were not suitable for transplant. Parsons’ family gave permission for his body to remain on life support so that the procedure could take place.
“Jim would have wanted to save as many people as he could with his death,” Parsons’ ex-wife Julie O’Hara, who made the decision along with their children and Parson’s sisters and mother, said in a statement. “And if he knew he could potentially save thousands and thousands of people by doing this, he would have had no hesitation.”
Prior to the surgery, a crossmatch compatibility test between the pig kidney and patient was performed to ensure a good tissue match. Once the match was determined, the kidneys were removed from the donor pig and processed for transplantation in a manner similar to human kidneys.
During the surgery itself, the brain-dead patient received immune-suppression therapy as would normally be used during a transplant procedure. The original kidneys were then removed and the pig kidneys transplanted into their place. The transplant included the attachments to the renal arteries and veins as well as the ureter, which carries urine from the kidney to the bladder.
The study was conducted with an eye to meeting the standards of a phase 1 clinical trial, so that the team at UAB can move to trials on living human beings more quickly, Locke explained.
“I felt that it was very important that this work be conducted in a rigorous scientific manner under the constraints of a study protocol,” she said. “And that it be allowed to be reviewed by our peers and published in a peer reviewed publication.”
Researchers at UAB hope to move to experimental transplants in living patients in a phase 1 clinical trial next year.
University of Alabama-Birmingham
This is one of several successful experimental xenotransplants that have occurred in the past few weeks. Earlier this month, the University of Maryland successfully transplanted a gene-edited pig heart into a living patient. NYU-Langone has also conducted two pig-kidney transplants with brain-dead patients.
However, unlike the UAB procedure, those other two kidney procedures involved attaching the organ to the outside of the patient, rather than in the same place as the kidney internally. Additionally, the pigs in these experiments, also developed by Revivicor, were from an earlier line that did not include all ten gene-edits as the pig in the UAB study.
With a successful procedure with a brain-dead patient that was conducted to clinical standards and a peer-reviewed study, Locke said that the next step is to move this procedure into phase 1 clinical trials involving living human patients. Locke said that she hopes they’ll have regulatory clearance to begin these studies by the end of 2022. From there, UAB intends to scale its facilities to enable hundreds of potential xenotransplants, which could potentially be available to the wider public in as little as five years “if we hit every milestone, no setbacks,” Locke said.
“We’ll certainly have to scale this up as we progress to the various phases of clinical trial and product development with the FDA,” she continued.
That will involve scaling up the pathogen-free facility where the pigs are bred and raised. For the phase one clinical trials, Locke estimates they will have enough for 10-20 trial participants. Phase 2 and 3 clinical trials will involve several hundred people. But by the time the kidney transplants have gone through the clinical trial process, she believes there will be organs that can help patients around the country.
“Certainly, within five years as we progress, I have no doubt given the commitment of United Therapeutics, we will be ramped up sufficiently to be able to provide organs,” she says.
Even further in the future, Locke says, the pigs at the UAB facility will be able to be used for multiple organ donations, where one pig might be able to provide a heart, live, kidneys and possibly lungs. And eventually she hopes the university will be able to collaborate with teams around the world to maximize the potential of the technology.
“We want to be able to help all patients achieve transplantation,” she added.
