Surgeon-scientists analyze the case of Lawrence Faucette, the second recipient of a genetically modified pig heart, to identify challenges to avoid rejection in future xenotransplants.
Summary
Surgeon-scientists at the University of Maryland School of Medicine published an analysis in Nature Medicine documenting the case of Lawrence Faucette, the second person in the world to receive a genetically modified pig heart transplant. Faucette, 58, who had end-stage heart disease and was ineligible for a traditional transplant, lived for 40 days before the transplanted heart began to fail due to rejection. The report details initial signs of rejection two weeks post-surgery and highlights lessons learned, including the role of antibodies in graft failure. Researchers emphasize the need for more effective immunosuppression strategies and view the case as a critical step in advancing xenotransplantation.
Key Takeaways
- Critical Insights from Pig Heart Rejection: The report highlights that rejection began about two weeks after transplantation, driven by a surge in anti-pig antibodies, despite efforts to minimize pre-existing antibodies.
- A Step Forward in Xenotransplantation: The study underscores progress in understanding immune rejection and surgical techniques, offering a roadmap for addressing challenges in future trials.
- Bravery Drives Innovation: The courage of Lawrence Faucette and his family provided invaluable scientific data, shaping future research aimed at overcoming immunological barriers in xenotransplantation.
Continuing advancements in the field of xenotransplantation, surgeon-scientists from the University of Maryland School of Medicine provided an extensive analysis on the second patient in the world to receive a genetically modified pig organ.
Lawrence Faucette, 58, received a pig heart at the University of Maryland Medical Center in 2023 to treat his end-stage heart failure. He lived for 40 days before choosing to forgo additional treatment after the transplant began to fail due to rejection.
The report documenting insights gleaned from Faucette’s experience, as the world’s second xeno heart transplant recipient, was published in the journal Nature Medicine. The paper documents initial signs of rejection of the 10 gene-edited pig heart on the first biopsy performed about two weeks after the surgery. It provides lessons learned and potential new pathways forward as xenotransplant surgeons prepare for upcoming clinical trials in the years ahead.
“We have taken another important step forward in the quest to address the global shortage of donor hearts, and we once again found that the porcine heart demonstrated excellent systolic and diastolic function during the initial weeks post-transplantation,” says study co-lead and first author Bartley P. Griffith, MD, who surgically transplanted the pig heart into both the first and second patient at the University of Maryland Medical Center, in a release.
Griffith is the Thomas E. and Alice Marie Hales Distinguished Professor in Transplant Surgery, the Department of Surgery’s Vice Chair of Innovation, and Clinical Director of the Cardiac Xenotransplantation Program at The University Of Maryland School Of Medicine.
“Thanks to the bravery of Mr. Faucette and his loving family, we have a clearer understanding of modifications we can make moving forward to achieve longer-term success,” Griffith says in a release.
A Critical Option for End-Stage Heart Disease
Faucette had end-stage heart disease and was deemed ineligible for a traditional transplant with a human heart due to his pre-existing peripheral vascular disease and complications with internal bleeding. This transplant was the only option available for Faucette who was facing near-certain death from heart failure.
“We are humbled by our experience, not only because of what we have learned but also from witnessing the strength and grace of our two patients and their families,” says study co-lead and corresponding author Muhammad M. Mohiuddin, MD, professor of surgery, program and scientific director of the Cardiac Xenotransplantation Program at The University Of Maryland School Of Medicine and president of International Xenotransplantation Association, in a release. “Their sacrifice yielded crucial scientific insights into how we and others should proceed to learn how to prevent graft failure from happening in future transplants.”
Future Research and Immune Challenges
Through their investigation, the study authors determined that this case underscores the need for continued research to overcome challenges such as antibody-mediated rejection. Despite selecting a patient with low pre-existing anti-pig antibodies, the transplant team found a surge in these antibodies, which caused damage to the heart and ultimately led to graft failure.
Further transplants may require more aggressive depletion and suppression of these antibodies. These investigations further elaborated on the influence of other immune-mediated mechanisms in graft failure.
“Despite setbacks related to immunological rejection after a few weeks, xenotransplantation and living-related organ donation remain our most viable pathways forward towards sustainable organ availability to meet the needs of our aging populations,” says Mark T. Gladwin, MD, the John Z. and Akiko K. Bowers Distinguished Professor and Dean of The University Of Maryland School Of Medicine and vice president for medical affairs at the University of Maryland, Baltimore, in a release. “We certainly faced similar challenges in the early days of solid organ transplantation. Our physician-scientists continue to work towards a better understanding of how to prevent porcine organ rejection despite aggressive immunosuppression and early successful surgical and hemodynamic outcomes.”
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