The surgery, performed by Professor Robert Montgomery’s team, linked the genetically modified organ to a 57-year-old brain-dead patient. the longest period so far recorded in the field of xenotransplantation of this type
Another step forward in the difficult path of xenotransplantation: the protagonists are the surgeons of the New York University Langone led by Professor Robert Montgomery, one of the pioneers in this field at an international level. After trying
The novelty compared to the attempted transplant two years ago is that the xenotransplantation performed represents, according to the authors, the longest period in which a genetically modified pig kidney has functioned in a human being. Faced with the now chronic shortage of organs for human transplantation, xenotransplantation is one of the alternative therapies that medicine has been experimenting with for a decade. There simply aren’t enough organs available for all those who need them, says Montgomery, who received himself a hepatitis C positive heart transplant in 2018. Too many people die due to lack of available organsand I strongly believe that xenotransplantation is a viable way to change that.
This therapy would deliver the advantage of a potentially unlimited source of organs, which can be transplanted on a schedule, of high quality from the point of view of the infectious profile and able to overcome even the hesitations of those who do not accept cadaveric donation. So many for the problems still to be overcome: immunological and physiological compatibility, biosafety, ethical and regulatory aspects.
The intervention
The surgery, performed on July 14 and led by Robert Montgomery, was the fifth xenograft performed at NYU Langone. The ongoing observation and study will continue until mid-September 2023. This work demonstrates that a pig kidney, with only one genetic modification and no drugs or experimental devices, can replace the function of a human kidney for at least 32 days without being rejected, explains Professor Montgomery, who had previously performed the first test in the world transplanting a genetically engineered pig kidney into a deceased human on September 25, 2021, followed by a second similar procedure on November 22, 2021.
Surgeons from the Transplant Institute also performed two genetically engineered pig heart transplants modified in the summer of 2022, after the one performed on January 11 of the same year on David Bennett by doctors at the University of Maryland Medical Center in Baltimore (the man died two months later).
The obstacles to overcome
The first hurdle to overcome in xenotransplantation is to prevent the so-called hyperacute rejection, which typically occurs a few minutes after an animal organ is connected to the human circulatory system. By deleting the gene encoding the biomolecule known as alpha 1,3 galactose or alpha-gal (identified as responsible for rapid antibody-mediated rejection of pig organs in humans), immediate rejection was avoided in all five xenografts at NYU Langone. In addition, the pig’s thymus gland, which is responsible for the education of the immune system, has been incorporated under the outer layer of the kidney to prevent new delayed immune responses.
The combination of modifications has been shown to prevent organ rejection while preserving kidney function. To ensure that the kidney function of the body was supported exclusively by pig kidney, both of the transplant recipient’s native kidneys were surgically removed. The transplanted pig kidney she started producing urine immediately without any signs of hyperacute rejection.
Observation phase
During the observation phase, the ICU staff maintained the patient’s circulatory support while the performance of the porcine kidney was monitored and sampled with weekly biopsies. Levels of creatinine, a waste product found in the blood and an indicator of kidney function, were in the optimal range during the duration of the study, and there was no evidence of rejection on the biopsy. This important research was made possible by the family of a 57-year-old man who chose to donate his body after being declared brain dead.
US data
In the US, there are More than 103,000 people on a transplant waiting list, nearly 88,000 of whom are waiting for a kidney, according to recent data from the Federal Organ Procurement and Transplantation Network (OPTN). In 2022, approximately 26,000 people received a kidney transplant. Meanwhile, nearly 808,000 people have end-stage kidney disease.
The kidney and thymus gland used in this procedure were purchased from a particular type of pig which, in December 2020, the US Food and Drug Administration (FDA) approved as potential source of human therapiesas well as food for people with alpha-gal syndrome, a meat allergy caused by a tick bite.
Minimized genetic modifications
While previous genetically modified pig organ transplants incorporated up to 10 genetic modifications, this latest study shows that a pig kidney with single gene knockout can still function optimally for at least 32 days without rejection. We have now gathered more evidence to show that, at least in the kidneys, deleting the gene that triggers hyperacute rejection alone may be sufficient along with clinically approved immunosuppressive drugs to successfully manage transplantation into a human for optimal, potentially long-term performance adds Professor Montgomery.
The NYU Langone team used standard immunosuppressive drugs for transplants combined with enhanced porcine cytomegalovirus screening (pCMV) in the donor pig to ensure safety. Recent studies have shown that pCMV can affect organ performance and potentially trigger organ failure. No pCMV was detected after 32 days and close surveillance was performed porcine endogenous retrovirus (PERV)along with six other viruses of interest.
The next steps
Monitoring of the pig kidney recipient will continue for another month. Additional data over the next few weeks will be analyzed further to develop a deeper understanding of this remarkable medical advance. We believe using a pig already deemed safe by the FDA in combination with what we have found so far in our xenotransplantation research brings us closer to the clinical trial phase adds Professor Montgomery. We know this procedure has the potential to save thousands of lives, but we want to ensure maximum safety and assistance as we move forwardhe concludes.
August 17, 2023 (change August 17, 2023 | 15:26)
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