CTI Annual Report 2023 | Page 40

NEWS

NEWS

These studies are supported by biotechnology pioneer United Therapeutics Corp ., which awarded a grant to UAB to launch the innovative xenotransplantation program . Revivicor Inc ., a subsidiary of United Therapeutics , provided the genetically modified pig that was the source of the investigational xenotransplant kidneys called UKidney™ . The pigs are raised in a secure , pathogen-free facility by UAB animal care experts and are regularly tested for porcine cytomegalovirus ( CMV ) and porcine endogenous retroviruses ( PERV ), including PERV-C . The pig used in this study tested negative for PERV-C and CMV .

Building upon previous successes This is the third study in UAB ’ s Parsons Model program and the second one to be peer-reviewed and published ( Dr . Locke ’ s team is in the process of publishing results from another Parsons Model study ). In an initial study last year , Dr . Locke and her research team demonstrated the model ’ s significant potential to propel the xenotransplantation field forward and help solve the kidney shortage crisis .

Each of the model ’ s studies have built upon the other and answered critical questions on the viability of pig kidney xenotransplantation . Specifically , for the two peer-reviewed , published studies :

• The original American Journal of Transplantation study from 2022 , named after Parsons , marked the first time a pig-to-human crossmatch was developed and validated . That step was important because federal requirements for human-to-human allotransplantation include a crossmatch and tissue compatibility prior to proceeding with a transplant .

• In the August 2023 JAMA Surgery publication , the decedent was stable when he presented for the study , which allowed Dr . Locke ’ s team to follow the investigation for seven days . Because the study subject was stable and the kidneys were in a favorable environment , there was no delay of kidney function – something that wasn ’ t the case in the first two studies .

As in the two previous studies , each stage of this third decedent xenotransplant study approximated the steps that would be taken in a Phase I clinical trial of xenotransplantation in living humans . “ At each of those steps , we were able to test that we do have the correct standard operating procedures in place and that we ’ re able to operationalize this in a meaningful , safe way ,” Dr . Locke said . “ That ’ s the ultimate goal – we want to achieve xenotransplant in a safe and efficacious way . We ’ re very hopeful that these data will provide further evidence that xenotransplantation is a viable and achievable solution to the organ shortage crisis that causes thousands of preventable deaths each year . The gap between supply and demand is that vast .”

Gene editing Gene editing in pigs to reduce immune rejection has made organ transplants from pigs to humans possible , an advancement that could offer help to thousands of people who face organ failure , disease , or injury . The pig kidneys used in the UAB studies come from pigs with 10 specific genetic modifications , each of which is intended to make the organs suitable for transplant into the human body .

The natural lifespan of a pig is 30 years , they are easily bred , and they have organs of similar size to humans . Genetically modified pig kidneys have been extensively tested in non-human primates . The addition of UAB ’ s preclinical human research model – the Parsons Model – now provides important information about the potential safety and efficacy of kidneys in human transplant recipients , including in clinical trials . “ Non-human primate research cannot answer whether the humanized pig kidneys will serve as a destination or bridge therapy ,” Dr . Locke said . “ Only human xenotransplantation can fully test this .”

LEGACY OF HOPE HONORED XENOTRANSPLANT RECIPIENT JIM PARSONS AS PART OF 2023 DONATE LIFE ROSE PARADE SPONSORSHIP

Legacy of Hope , Alabama ’ s organ procurement organization , supported its mission to promote organ , eye , and tissue donation by sponsoring the 2023 Donate Life Rose Parade float . At the event , Legacy of Hope honored Alabamian Jim Parsons , whose floragraph was displayed on the float along with those of other donors from around the country .

38 UAB CTI Report