NEW YORK, NY, APRIL 24, 2024— Surgeons at NYU Langone Health performed the first-ever combined mechanical heart pump and gene-edited pig kidney transplant surgery in a 54-year-old woman with heart and kidney failure—a confluence of advances that showcase the possibility and hope of modern medicine.
Doctors performed this feat in two stages: first surgically implanting the heart pump days before embarking on the landmark transplant, which included a gene-edited pig kidney and the pig's thymus gland to aid against rejection. Before the procedure, patient Lisa Pisano, a New Jersey native, faced heart failure and end-stage kidney disease that required routine dialysis. She was not a candidate for heart and kidney transplants because several chronic medical conditions significantly reduced the likelihood of a good outcome and there aren't enough organs for those in need.
Despite these adversities, Pisano has thrived from the love of her grandchildren and eagerly wants to watch them grow up.
"All I want is the opportunity to have a better life," she said. "After I was ruled out for a human transplant, I learned I didn't have a lot of time left. My doctors thought there may be a chance I could be approved to receive a gene-edited pig kidney, so I discussed it with my family and my husband. He has been by my side throughout this ordeal and wants me to be better."
To date, there have been no documented instances of anyone with a mechanical heart pump receiving an organ transplant of any kind. It is only the second known transplant of a gene-edited pig kidney into a living person, and the first with the thymus combined.
"It is incredible to consider the scientific achievements that have led to our ability to save Lisa's life, and what we are endeavoring to do as a society for everyone in need of a life-saving organ," said Robert Montgomery, MD, DPhil, who led the transplant surgery and who is the H. Leon Pachter, MD, Professor of Surgery; chair of the Department of Surgery; and director of the NYU Langone Transplant Institute. "This could not have been done without the dedication and skill of the many talented physicians, researchers, nurses, health administrators, and perioperative care teams at NYU Langone Health, and the numerous pioneers who came before us."
Nearly 104,000 people are on the waiting list for a transplant, with 89,360 of those waiting for a kidney. Nearly 808,000 people in the United States have end-stage kidney disease but only about 27,000 were able to receive a transplant last year.
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About the Procedures
The series of procedures were performed by two separate surgical teams over the course of nine days.
In the first procedure, surgeons implanted the heart pump, a device called a left ventricular assist device (LVAD), which is typically used in patients who are awaiting heart transplantation or otherwise ruled ineligible to receive a heart transplant.
Without a heart pump Pisano's life expectancy would have been measured in days or weeks.
Nader Moazami, MD, chief of the Division of Heart and Lung Transplantation and Mechanical Circulatory Support for the Department of Cardiothoracic Surgery at NYU Grossman School of Medicine, and Deane E. Smith, MD, director of mechanical circulatory support, performed the LVAD surgery on April 4, 2024, in NYU Langone's Kimmel Pavilion in New York.
The second procedure was a xenotransplant, which is a transplant of an organ between different species. Dr. Montgomery led the xenotransplant on April 12, 2024.
Pisano had high levels of harmful antibody to human tissue, but not to gene-edited pig organs. It would have taken years for her to find a match for a human kidney transplant. Dr. Montgomery approached United Therapeutics Corporation and determined an investigational gene-edited pig kidney with thymus was available and matched. Although chronic kidney failure typically rules patients out from receiving an LVAD, the hope of the transplant preventing her from needing dialysis was a key consideration.
"Without the possibility of a kidney transplant, she would not have been eligible as a candidate for an LVAD due to the high mortality in patients on dialysis with heart pumps," said Dr. Moazami. "This unique approach is the first time in the world that LVAD surgery has been done on a dialysis patient with a subsequent plan to transplant a kidney. The measure for success is a chance at a better quality of life and to give Lisa more time to spend with her family."
Pisano received the organ from a pig genetically engineered to disrupt, or "knock out," the gene responsible for the production of a sugar known as alpha-gal. In previous studies at NYU Langone, it was demonstrated that removing alpha-gal was sufficient to prevent an antibody reaction that can cause immediate, or hyperacute, rejection of the xeno-organ. The donor pig's thymus gland, which is responsible for educating the immune system, was surgically placed under the covering of the kidney to reduce the likelihood of rejection. The xenokidney and the thymus tissue combined are called a UThymoKidney™. The gene edits, pig breeding, and production of the investigational UThymoKidney™ used in this procedure were performed by United Therapeutics Corporation. No other unapproved devices or medications were used in the procedure.
"By using pigs with a single genetic modification, we can better understand the role one key stable change in the genome can have in making xenotransplantation a viable alternative," said Dr. Montgomery. "Since these pigs can be bred and do not require cloning like more-complex gene edits, this is a sustainable, scalable solution to the organ shortage. If we want to start saving more lives quickly, using fewer modifications and medications will be the answer."
The effort required rigorous preparation, clearance by NYU Langone's institutional review board, and approval by the FDA through its Expanded Access Program—sometimes called "compassionate use" and meant for patients who have a serious or immediately life-threatening condition.
Additional investigators in the xenotransplant included Adam Griesemer, MD; Jeffrey M. Stern, MD; Bonnie E. Lonze, MD, PhD; Nicole M. Ali, MD; Sapna A. Mehta, MD; Vasishta Tatapudi, MD; Massimo Mangiola, PhD; Elaina Weldon, MSN, NP; Karen Khalil, PharmD; Jacqueline Kim, MD; Ian S. Jaffe; Imad Aljabban, MD; Aprajita Mattoo, MD; Rebecca Esker, PharmD; Nikki Lawson, RN; Jef Boeke, PhD; Brendan Keating, PhD; and Alexandre Loupy, MD, PhD, director of the Paris Institute for Transplant and Organ Regeneration.
The NYU Langone Transplant Institute collaborated with David Sachs, MD, and Megan Sykes, PhD, of the Columbia Center for Translational Immunology (CCTI) at Columbia University Irving Medical Center. They both helped to develop a pig thymus–kidney concept with the intent of reducing the amount of immunosuppression. This procedure marked the first-ever human transplant of a pig-derived thymokidney.
NYU Langone Health acknowledges United Therapeutics Corporation for the UThymoKidney™ and financial support provided for xenotransplantation research initiatives and this procedure, as well as the support of Apellis Pharmaceuticals Inc.'s Compassionate Use Program, which provided Empaveli®, also known as pegcetacoplan, a medicine used in the off-label treatment to prevent rejection of the organ.
Progress in Xenotransplantation
This complex intervention marks the sixth human xenotransplant surgery performed by the NYU Langone Transplant Institute and orchestrated by Dr. Montgomery, who has spent much of his career studying innovative approaches to expanding the organ supply and performed the world's first gene-edited pig-to-human organ transplant on September 25, 2021, in a neurologically deceased person with a beating heart. The same gene-edited pig kidney and thymus were used in that procedure and in a second similar procedure on November 22, 2021. Surgeons at NYU Langone then performed two gene-edited pig heart transplants in summer 2022. Last year, a 61-day study of a gene-edited pig kidney xenotransplant in a recently deceased man showed optimal performance with standard-of-care immunosuppression.
The NYU Langone Transplant Institute has performed more xenotransplantation surgeries in humans than any other institution to date. Before this most recent surgery, however, five were done using a special protocol involving recently deceased people, in collaboration with their families, to study the effectiveness and viability of gene-edited pig organs in humans before transplanting them into living people.
"Without the generosity and altruism of those who participated in our series of decedent model studies, this moment in transplantation would not have been possible," said Dr. Montgomery. "We eagerly await the opportunity to participate in clinical trials, under the FDA's guidance, to continue learning more about the possibility of a new, sustainable source of organs for all those without much time left."
About the NYU Langone Transplant Institute
The NYU Langone Transplant Institute offers the highest-quality kidney and lung transplantation programs in the nation, according to federal quality data, while the heart and liver transplant programs stand out in national survival rates and in their success getting patients off the waitlist. In 2023, the institute performed 576 organ transplants. NYU Langone's heart, kidney, liver, lung, and pancreas transplant programs are approved by the Centers for Medicare & Medicaid Service (CMS), which means they have met the stringent volume, process, quality, and survival outcome requirements of CMS regulation.
