CTI Annual Report 2022 | Page 6

UAB PERFORMS FIRST CLINICAL-GRADE PIG-TO-HUMAN KIDNEY XENOTRANSPLANT

INNOVATION

INNOVATION

UAB PERFORMS FIRST CLINICAL-GRADE PIG-TO-HUMAN KIDNEY XENOTRANSPLANT

facility , the pig kidneys were modified with 10 key gene edits that made them suitable for direct clinical-grade therapeutic use in humans . The process demonstrated how such a transplant would work in a real-world application , while providing crucial safety data testing its efficacy .
The Organ Shortage Crisis The availability of organs is a continual challenge , especially with kidneys . Some 800,000 Americans are living with kidney failure on dialysis – and more than 90,000 are on the transplant waiting list – but fewer than 25,000 kidney transplants are performed each year . Most people who need a kidney never even make it to the waiting list .
Current forms of living- and deceased-donor kidney transplants work well , curing end-stage kidney disease more than 95 % of the time . But there simply aren ’ t enough donor organs to go around . Preliminary research shows that many people have antibody profiles that are compatible with pig organs . Between xenografts and human-to-human allotransplantation , the kidney transplant waiting list could be eliminated someday .
In September 2021 , the UAB Comprehensive Transplant Institute ( CTI ) achieved a major first in xenotransplantation . Genetically modified , clinical-grade pig kidneys were transplanted into a brain-dead human , as part of research that one day could overcome the worldwide organ shortage .
The study marks the first peer-reviewed , published research to establish brain death as a viable preclinical human model . CTI Director Jayme Locke , MD , MPH , was lead investigator for the study , published Jan . 20 , 2022 , in the American Journal of Transplantation .
The recipient ’ s native kidneys were removed first . Once transplanted , the pig kidneys filtered blood , produced urine , and – importantly – were not immediately rejected . The kidneys remained viable until the study was ended , 77 hours after transplant . Procured at a pathogen-free
“ This game-changing moment in the history of medicine represents a paradigm shift and a major milestone in the field of xenotransplantation , which is arguably the best solution to the organ shortage crisis ,” Dr . Locke says . “ We have bridged critical knowledge gaps and obtained the safety and feasibility data necessary to begin a clinical trial in living humans with end-stage kidney failure disease .”
Gene Editing & Safety Testing Gene editing in pigs to reduce immune rejection has made organ transplants from pigs to humans possible , and genetically modified pig kidneys have been extensively tested in non-human primates . Evaluating genetically modified pig kidneys in a human preclinical model study may provide important information about the potential safety and efficacy of kidneys in human transplant recipients , including in clinical trials .
“ This human preclinical model is a way to evaluate the safety and feasibility of the pig-to-non-human primate model , without risk to a living
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