UM School of Medicine Researchers Identify Challenges to Overcome to Avoid Rejection in Future Xenotransplants
Continuing significant 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 Mr. Faucette’s experience, as the world’s second xeno heart transplant recipient, was published today 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 important 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,” said study co-lead and first author Bartley P. Griffith, MD, who surgically transplanted the pig heart into both the first and second patient at UMMC. Dr. 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 UMSOM. “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.”
Mr. 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 Mr. 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,” said study co-lead and corresponding author Muhammad M. Mohiuddin, MD, Professor of Surgery, Program and Scientific Director of the Cardiac Xenotransplantation Program at UMSOM and President of International Xenotransplantation Association. “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.”
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 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,” said Mark T. Gladwin, MD, the John Z. and Akiko K. Bowers Distinguished Professor and Dean of UMSOM and Vice President for Medical Affairs, University of Maryland, Baltimore. “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.”
Other UMSOM faculty co-authors of this study include: Avneesh K Singh, PhD, Alison Grazioli, MD, Kapil Saharia, MD, Andy Tully, MD, Javier Galindo, MD, Kapil K. Saharia, MD, Erik R. Strauss, MD, Patrick N. Odonkor, MD, Brittney Williams, MD, Henry J. Silverman, MD, Allen Burke, MD, Cinthia B. Drachenberg, MD,, Chris L. Wells, PT, PhD, Timm Dickfeld, MD, PhD, Susie N. Hong, MD, Albert J. Hicks III, MD, Manjula Ananthram, MD, Anuj Gupta, MD, Robert H. Christenson, PhD, Tianshu Zhang, PhD, and Bradley Taylor, MD.
“We continue to learn so much from these pioneering surgeries, and we are grateful to United Therapeutics for their support of our work as we help move the field of xenotransplantation closer to becoming a clinical reality,” said study co-author Christine Lau, MD, MBA, the Dr. Robert W. Buxton Professor, Chair of the Department of Surgery at UMSOM, and Surgeon-in-Chief at UMMC.
Added Bert W. O’Malley, MD, UMMC President and CEO: “Academic medicine thrives on bold innovation, rigorous research, and the unwavering courage of patients and their families. The insights gained from Mr. Faucette’s journey, alongside the learnings from our first pig heart transplant recipient, serve as a beacon guiding our ongoing quest to overcome the hurdles of this transformative medical advancement. We continue to be inspired by Mr. Faucette, not only by his drive to advance the science of xenotransplantation but also by the gratitude he expressed to the UMMC team members who cared for him.”
Disclosures: United Therapeutics, Inc., provided funding to the University of Maryland Foundation to help defray the cost of this transplant. Revivicor, Inc provided the genetically-modified pig source for the organ, and Eledon Pharmaceuticals provided the Tegoprubart antibody.
