Presenting a path forward for future genetically-modified pig heart transplants: lessons learned from second patient

(Press-News.org) 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: “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.  

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.2 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically based care for nearly 2 million patients each year. The School of Medicine has nearly $600 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The combined School of Medicine and Medical System ("University of Maryland Medicine") has an annual budget of over $6 billion and an economic impact of nearly $20 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-up companies. In the latest U.S. News & World Report ranking of the Best Medical Schools, published in 2023, the UM School of Medicine is ranked #10 among the 92 public medical schools in the U.S., and in the top 16 percent (#32) of all 192 public and private U.S. medical schools. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu

About the University of Maryland Medical Center

The University of Maryland Medical Center (UMMC) is comprised of two hospital campuses in Baltimore: the 800-bed flagship institution of the 11-hospital University of Maryland Medical System (UMMS) and the 200-bed UMMC Midtown Campus. Both campuses are academic medical centers for training physicians and health professionals and for pursuing research and innovation to improve health. UMMC's downtown campus is a national and regional referral center for trauma, cancer care, neurosciences, advanced cardiovascular care, and women's and children's health, and has one of the largest solid organ transplant programs in the country. All physicians on staff at the downtown campus are clinical faculty physicians of the University of Maryland School of Medicine. The UMMC Midtown Campus medical staff is predominately faculty physicians specializing in a wide spectrum of medical and surgical subspecialties, primary care for adults and children and behavioral health. UMMC Midtown has been a teaching hospital for 140 years and is located one mile away from the downtown campus. For more information, visit umm.edu.

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: “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.  

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.2 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically based care for nearly 2 million patients each year. The School of Medicine has nearly $600 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The combined School of Medicine and Medical System ("University of Maryland Medicine") has an annual budget of over $6 billion and an economic impact of nearly $20 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-up companies. In the latest U.S. News & World Report ranking of the Best Medical Schools, published in 2023, the UM School of Medicine is ranked #10 among the 92 public medical schools in the U.S., and in the top 16 percent (#32) of all 192 public and private U.S. medical schools. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu

About the University of Maryland Medical Center

The University of Maryland Medical Center (UMMC) is comprised of two hospital campuses in Baltimore: the 800-bed flagship institution of the 11-hospital University of Maryland Medical System (UMMS) and the 200-bed UMMC Midtown Campus. Both campuses are academic medical centers for training physicians and health professionals and for pursuing research and innovation to improve health. UMMC's downtown campus is a national and regional referral center for trauma, cancer care, neurosciences, advanced cardiovascular care, and women's and children's health, and has one of the largest solid organ transplant programs in the country. All physicians on staff at the downtown campus are clinical faculty physicians of the University of Maryland School of Medicine. The UMMC Midtown Campus medical staff is predominately faculty physicians specializing in a wide spectrum of medical and surgical subspecialties, primary care for adults and children and behavioral health. UMMC Midtown has been a teaching hospital for 140 years and is located one mile away from the downtown campus. For more information, visit umm.edu.

 

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