What makes this study unique ? This study is the :
• First peer-reviewed , published study of a genetically modified pig kidney transplanted into the body of a brain-dead human recipient
• First such study on a pig-to-human kidney xenotransplant using clinical-grade , genetically modified kidneys that have undergone 10 key gene edits , which may make the kidneys suitable for therapeutic use in humans
• First validation of a UAB-developed test for compatibility before xenotransplantation
• First peer-reviewed , published study to establish brain death as a viable preclinical human model
Notably , the study was designed and conducted to meet standards directly comparable to those that would apply to a Phase I clinical trial . As much as possible , it mirrored every step of a conventional transplant between humans . Importantly , this study included removing the human brain-dead recipient ’ s native kidneys before replacing them with genetically modified pig kidneys .
When would UAB be able to take this into a living human clinical trial ? UAB physicians already are working on the next steps to begin a clinical trial or compassionate or emergency use of the pig kidneys in living humans . Two major approvals will be required .
First , the U . S . Food and Drug Administration ( FDA ) must approve an investigator-initiated Investigational New Drug Application to administer the biological product – genetically modified pig kidneys – to humans . Secondly , UAB ’ s Institutional Review Board ( IRB ) for Human Use must review and approve the proposed clinical study before the start of a Phase I trial to test whether this transplant is safe in living humans .
“ We anticipate getting additional guidance from the FDA soon about what they think is appropriate ,” Dr . Locke says . “ It is quite possible that they ’ ll want us to do additional studies in the human brain-dead model . We plan to move this model forward , and look to perform additional transplants in this model , to continue collecting and compiling data to make the case that we are ready to do this in living people .”
What are the next steps before the gene-edited pig kidneys could be transplanted into humans ? UAB and other academic collaborators continue to generate data , including thorough pre-clinical work , as we advance the science behind xenotransplantation . “ We are continuing to work with the FDA on a clinical and regulatory path forward ,” Dr . Locke says . “ Our published study gave us answers to critical safety questions that would be needed before performing the transplant in living persons .”
How soon before we could safely perform xenotransplantation in living humans ? An exact timeframe will depend on approvals , successes in future studies , and progress with clinical trials . “ We are confident that the success of this transplant , our published findings , and successful xenotransplants at other institutions are getting us as close as possible to this being a viable option for patients in need ,” Dr . Locke says .
Why pigs ? What similarities exist between pigs and humans ? Pig kidneys are very similar to human kidneys in their makeup and are about the same size . “ When you think about trying to ramp up xenotransplantation in relatively short order and keep pace with the demand , the pig offers a great opportunity for that ,” Dr . Locke says . “ Of course , pig organs are quite naturally foreign to the human immune system , so these 10 gene edits are necessary to make a pig kidney a bit more human . This allows the human immune system , supported by standard immunosuppression drugs , to tolerate the pig kidney and sustain the person after transplant .”
Will xenotransplantation replace allotransplantation ( human-to-human transplants )? No , xenotransplantation is meant to be complementary . However , pig xenografts for compatible people , combined with living- and deceaseddonor allotransplantation , could mean the end of the kidney transplant waiting list , Dr . Locke says . “ Xenotransplantation is simply filling the gap that allotransplantation cannot quite fill , but it needs to be done in concert .”
INNOVATION uabmedicine . org / refertransplant 11