The field of xenotransplantation is gaining momentum as recent pig kidney transplants demonstrate promising outcomes, offering potential solutions to the critical shortage of human organs. These advancements mark significant steps toward making animal-to-human transplants a viable option for patients with end-stage organ failure.
Landmark Cases Highlight Progress
Towana Looney, a 53-year-old woman from Alabama, has become the longest-living recipient of a gene-edited pig kidney, surpassing 60 days post-transplant. Performed at NYU Langone Health, the transplant represents a major leap forward in xenotransplantation. Looney, who had been on dialysis for eight years due to kidney failure stemming from pregnancy complications and a prior kidney donation to her mother, is now thriving with the new organ. According to Dr. Robert Montgomery, director of the NYU Langone Transplant Institute, Looney's kidney function is "absolutely normal."
Adding to this progress, Tim Andrews, a 66-year-old man from New Hampshire, received a genetically-edited pig kidney at Massachusetts General Hospital (MGH). Andrews, who suffered from end-stage kidney disease and had been on dialysis for two years, is now dialysis-free and recovering well. Dr. Tatsuo Kawai, the lead surgeon at MGH, expressed optimism about the potential of genetically-edited pig organs as a long-term solution for patients.
FDA Approves Clinical Trial
Further validating the field, United Therapeutics received FDA approval to begin a clinical trial of its UKidney, a gene-edited porcine kidney. This trial marks the first formal study of xenotransplantation and will initially involve six patients with end-stage kidney disease, with the possibility of expanding to 50 patients if the initial results are promising. Leigh Peterson, PhD, Executive Vice President at United Therapeutics, emphasized the company's goal to increase the availability of transplantable organs and offer an alternative to a lifetime on dialysis.
Addressing the Organ Shortage
The need for alternative organ sources is dire. Over 100,000 people are on the U.S. transplant list, with the majority needing a kidney. Thousands die each year while waiting for a suitable organ. Xenotransplantation offers a potential solution to this crisis by utilizing genetically modified pig organs that are less likely to be rejected by the human body.
Genetic Modifications and Immunosuppression
The pig kidneys used in these transplants undergo extensive genetic modifications to enhance compatibility with the human immune system. For example, the kidney Towana Looney received had 10 genetic edits. Similarly, EGEN-2784, the porcine kidney developed by eGenesis and transplanted into Tim Andrews, includes gene edits to knock out pig genes related to hyperacute rejection and the addition of human genes related to modulation of rejection. In addition to genetic modifications, patients receive immunosuppression regimens to prevent rejection. Tim Andrews, for instance, received tegoprubart, an investigational monoclonal antibody targeting the CD40L pathway.
Challenges and Future Directions
Despite these successes, challenges remain. Two patients who received pig hearts and one who received a pig kidney in earlier experiments died within two months of the transplant. However, researchers are learning from these cases and refining their techniques. As Dr. Kawai noted, "Although we have a long way to go to make that a reality, this transplant is an important next step."
The FDA's Expanded Access Protocol, also known as compassionate use, has allowed for these experimental transplants in patients with limited options. As more data become available and clinical trials progress, xenotransplantation may offer a transformative solution to the organ shortage crisis, providing hope for thousands of patients with end-stage organ failure.
