Tag: xenotransplantation

Categories : Genetics TransplantsTags :

Pig-to-human Kidney Xenotransplant is the Longest Successful One Yet

On By ModernMedia
Photo by Natanael Melchor on Unsplash

Surgeons at NYU Langone Health have transplanted a genetically engineered pig kidney that continues to function well after 32 days in a man declared dead by neurologic criteria and maintained with a beating heart on ventilator support. This represents the longest period that a gene-edited pig kidney has functioned in a human, and the latest step toward the advent of an alternate, sustainable supply of organs for transplant.

Led by Robert Montgomery, MD, DPhil, the procedure was performed on July 24, 2023 and marks the fifth xenotransplant performed at NYU Langone. Observation is ongoing and the study will continue through mid-September 2023.

“This work demonstrates a pig kidney – with only one genetic modification and without experimental medications or devices – can replace the function of a human kidney for at least 32 days without being rejected,” said Dr Montgomery, who had previously performed the world’s first genetically modified pig kidney transplant into a human decedent in 2021.

Removing single troublesome gene

The first hurdle to overcome in xenotransplants is preventing so-called hyperacute rejection, which typically occurs just minutes after an animal organ is connected to the human circulatory system. By “knocking out” the gene that encodes the biomolecule known as alpha-gal, responsible for a rapid antibody-mediated rejection of pig organs by humans, immediate rejection has been avoided in all five xenotransplants at NYU Langone. Additionally, the pig’s thymus gland, which is responsible for educating the immune system, was embedded underneath the outer layer of the kidney to stave off novel, delayed immune responses. The combination of modifications has been shown to prevent rejection of the organ while preserving kidney function.

To ensure the body’s kidney function was sustained solely by the pig kidney, both of the transplant recipient’s native kidneys were surgically removed. One pig kidney was then transplanted and started producing urine immediately without any signs of hyperacute rejection. During the observation phase, intensive care clinical staff maintained the decedent on support while the pig kidney’s performance was monitored and sampled with weekly biopsies. Levels of creatinine, a bodily waste product found in the blood and an indicator of kidney function, were in the optimal range during the length of the study, and there was no evidence on biopsy of rejection.

The surgery was the latest in a larger study approved by a specific research ethics oversight board at NYU Langone and was performed after consultation with the New York State Department of Health. This important research, which study leaders say could save many lives in the future, was made possible by the family of a 57-year-old male who elected to donate his body after a brain death declaration and a circumstance in which his organs or tissues were not suitable for transplant.

A big leap toward a new organ source

“There are simply not enough organs available for everyone who needs one,” said Dr Montgomery, who received a hepatitis C-positive heart transplant himself in 2018. “Too many people are dying because of the lack of available organs, and I strongly believe xenotransplantation is a viable way to change that.”

The kidney and thymus gland used in this procedure were procured from a GalSafeTM pig, an animal engineered by Revivicor, Inc., a subsidiary of United Therapeutics Corporation. In December 2020, the U.S. Food and Drug Administration (FDA) approved the GalSafe pig as a potential source for human therapeutics as well as a food source for people with alpha-gal syndrome, a meat allergy caused by a tick bite.

Less may be more

While previous genetically engineered pig organ transplants have incorporated up to 10 genetic modifications, this latest study shows that a single-gene knockout pig kidney can still perform optimally for at least 32 days without rejection.

“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,” said Dr Montgomery.

The NYU Langone team used standard transplant immunosuppression medications combined with enhanced screening of porcine cytomegalovirus (pCMV) in the donor pig to ensure safety. Recent studies have shown pCMV may affect organ performance and potentially trigger organ failure. No pCMV was detected after 32 days, and close surveillance of porcine endogenous retrovirus (PERV), along with six other viruses of interest, was performed.

Next steps

Monitoring of the pig kidney recipient will continue for another month with permission from the family, ethics committee approval and continued support from United Therapeutics. The additional data from the next several weeks will be analyzed further to develop a deeper understanding of this unique medical advance.

“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,” said Dr Montgomery. “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.”

Source: NYU Langone Health

Categories : TransplantsTags :

Two Pig Kidneys Transplanted into Human

On By ModernMedia
Photo by Robina Weermeijer on Unsplash

In a new study published in the American Journal of Transplantation, researchers report that they successfully transplanted two kidneys from a genetically modified pig into a human recipient who had suffered brain death.

The use of pig organs, genetically modified to enable transplantation into humans, could ease the shortage of available donor organs for transplantation and prevent thousands of deaths that result each year due to a shortage of organs. Recently, a US man became the first human recipient of a genetically modified pig heart.

This study used a novel preclinical human model to answer numerous critical safety questions. No hyperacute rejection was seen for the 74 hours until termination. No chimerism or transmission of porcine retroviruses was detected. Longitudinal biopsies revealed thrombotic microangiopathy that did not progress in severity, without evidence of cellular rejection or deposition of antibody or complement proteins. Although the xenografts produced variable amounts of urine, creatinine clearance did not recover. Whether renal recovery was impacted by the milieu of brain death and/or microvascular injury remains unknown.

The study provides important insights and identifies several areas where additional research is needed before xenotransplantation can be used to help address the current organ shortage.

“This study provides knowledge that could not be generated in animal models and moves us closer to a future where organ supply meets the tremendous need,” said senior author Jayme E. Locke, MD, MPH, of the University of Alabama at Birmingham.

Source: Wiley

Categories : Cardiovascular DiseaseTags : 1 Comment

Patient Doing Well after World-first Pig Heart Transplant

On By ModernMedia
Photo by Piron Guillaume on Unsplash

David Bennett, a 57 year old US man, is doing well after being the world’s first human transplant of a pig heart, according to the man’s son, David Bennett Jr.

When his father first told him of the pig heart option, his son was incredulous, telling the BBC: “I didn’t believe him, I thought he was suffering from delirium at first.”

However, when he did some research on the work done, he realised it was a reality and that they were “walking into the unknown”.

He added that according to Dr Bartley Griffith, who performed the surgery, his father has a good prognosis of 6–9 months. The experimental seven-hour procedure at the University of Maryland Medical Center in Baltimore was considered the last hope of saving Mr Bennett’s life, though it is currently unclear what his long-term chances of survival are. 

“It was either die or do this transplant,” Mr Bennett explained a day before the surgery, adding that it was his “last choice”.

Dr Griffith said heart failure and an irregular heartbeat made him ineligible for a human heart transplant or a heart pump.

Xenotransplantation, as these inter-species transplants are called, have failed, largely because patients’ bodies quickly rejected the animal organ. Notably, in 1984, Baby Fae, a dying infant, lived 21 days with a baboon heart. 

What makes this attempt different is that the Maryland surgeons used a heart from a pig that had been genetically modified to remove a sugar in its cells that’s responsible for that hyper-fast organ rejection. Many biotech companies are working on adapting pig organs for xenotransplantation.

“I think you can characterise it as a watershed event,” Dr David Klassen, chief medical officer at the United Network for Organ Sharing (UNOS), which oversees the US transplant system.

Dr Klassen nevertheless cautioned that it’s only a first tentative step into exploring whether xenotransplantation might finally work this time.

The Food and Drug Administration, which oversees such experiments, allowed the surgery under what’s called a “compassionate use” emergency authorisation, available when a patient with a life-threatening condition has no other options.

Surgeon Bartley Griffith said the surgery would bring the world “one step closer to solving the organ shortage crisis”. At present, 17 people die every day in the US waiting for a transplant, with more than 100 000 reportedly on the waiting list. A record 3800 heart transplants were done last year, according to the UNOS.

Source: BBC News