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SSurgeons at New York University Langone Health have performed the first surgery to combine a mechanical heart pump with a gene-edited pig kidney transplant. The patient is a 54-year-old woman with heart and kidney failure, and the surgery represents a promising combination of advances in modern medicine.
The doctors performed the feat in two stages. First, the heart pump was first surgically implanted, days before embarking on a breakthrough transplant involving a pig kidney and pig thymus that had been gene-edited to prevent rejection. Before the surgery, patient Lisa Pisano from New Jersey was facing heart failure and end-stage renal disease requiring regular dialysis. She is not a candidate for heart and kidney transplants because several chronic medical conditions greatly reduce the chance of a good outcome, and there are not enough organs for those who need them. There was no.
Despite these adversities, Pisano thrives on the love of his grandchildren and is eager to watch them grow.
“All I want is a chance to live a better life,” she said. “After being ruled out for a human transplant, I realized I didn't have much time left. Doctors told me I might be approved for a gene-edited pig kidney transplant. I thought about it, so I discussed it with my family and my husband. He has been by my side throughout this whole ordeal and wants me to get better.”
To date, there are no recorded cases of people wearing mechanical heart pumps receiving any type of organ transplant. This is the second time that a gene-edited pig kidney has been transplanted into a living human, and the first to be combined with a thymus gland.
“It's incredible to think about the scientific achievements that led to our ability to save Lisa's life and what we as a society are going to do for everyone who needs life-saving organs.” said Robert Montgomery, MD, who led the project. Who is H. Leon Pachter, MD, Professor of Transplant Surgery and Surgery?chair surgeryDirector of the Langone Transplant Institute, New York University; “This would not be possible without the dedication and skill of NYU Langone Health's many talented physicians, researchers, nurses, health administrators, perioperative care teams, and many others who have pioneered before us. would not have been possible.”
There are nearly 104,000 people on the transplant waiting list, of which 89,360 are waiting for a kidney transplant. Nearly 808,000 people in the United States have end-stage kidney disease, but only about 27,000 received a transplant last year.
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About the procedure
The series of surgeries were performed over nine days by two separate surgical teams.
During the first surgery, surgeons implanted a heart pump, a device called a left ventricular assist device (LVAD). This device is typically used for patients who are waiting for a heart transplant or who have been determined not to be eligible for a heart transplant.
Without a heart pump, Pisano's life expectancy would have been measured in days or even weeks.
Video: Transplant surgeons Dr. Robert Montgomery and Lisa Pisano discuss the groundbreaking surgery that gave Pisano a better chance at life.
Dr. Nader Moazami, Head of Heart and Lung Transplantation and Mechanical Circulatory Support Cardiothoracic surgery Dean E. Smith, M.D., MD and director of mechanical circulatory support at NYU Grossman School of Medicine, performed the LVAD surgery on April 4, 2024 at NYU Langone College Kimmel Pavilion in New York.
The second step is xenotransplantation, which is the transplantation of organs between different species. Dr. Montgomery led the xenotransplant on April 12th.
Pisano had high levels of harmful antibodies against human tissue, but not against gene-edited pig organs. It would take years for her to find a candidate for a human kidney transplant. Dr. Montgomery consulted United Therapeutics Corporation and determined that gene-edited research pig kidneys with thymus glands were available and suitable. Chronic renal failure typically precludes a patient from receiving her LVAD, but the hope that the transplant would eliminate the need for dialysis was an important consideration.
“Without the possibility of a kidney transplant, she would not have been an eligible candidate for an LVAD, as the mortality rate for patients receiving dialysis using a heart pump is high,” Dr. Moazami said. “This unique approach marks the first time in the world that LVAD surgery has been performed on a dialysis patient planning a kidney transplant. The measure of success is that it improves quality of life and gives Lisa time to spend with her family. It’s about giving them the opportunity to grow.”
Pisano received organs from pigs that had been genetically engineered to disrupt, or “knock out,” the gene responsible for producing a sugar known as alpha-gal. Previous research at New York University Langone demonstrated that removing alpha-gal is sufficient to prevent antibody responses that can cause immediate or hyperacute rejection of foreign organs. . The donor pig's thymus gland, which is responsible for “educating” the immune system, was surgically placed under a kidney cover to reduce the chance of rejection. The combination of xenogeneic kidney and thymus tissue is called UThymoKidney. Gene editing, pig breeding, and production of the investigational drug UThymoKidney used in this procedure were performed by United Therapeutics Corporation. No other unapproved devices or drugs were used in this procedure.
“By using pigs with a single genetic modification, we can better understand how one key stable change in the genome could play a role in making xenotransplantation a viable alternative. “We'll be able to do that,” Dr. Montgomery said. “Because these pigs are fertile and do not require cloning, such as more complex gene editing, this is a sustainable and scalable solution to organ shortages. Start saving more lives sooner. If so, the answer may be to reduce the use of modifications and drugs.”
The initiative involved careful preparation, approval by NYU Langone's Institutional Review Board, and an expanded access program (sometimes called “compassionate use”) for critically ill or immediately deceased patients. ) required approval by the U.S. Food and Drug Administration (FDA). threatening condition.
Additional xenotransplant investigators included Adam Griesemer, MD; Jeffrey M. Stern, MD. Bonnie E. Ronze, MD. Nicole M. Ali, MD. Sapna Mehta, MD. Vasishta Tatapudi, Maryland. Dr. Massimo Mangiola; Elaina Weldon, MSN, NP; Karen Kalil, PharmD; Dr. Jacqueline Kim. Ian S. Jaffe; Imad Aljaban, MD; Arajita Mattoo, MD; Rebecca Esker, Pharm.D. Nikki Lawson, RN. Dr. Jeff D. Bouquet; Dr. Brendan Keating; Alexandre Loupy, MD, Director of the Paris Institute for Transplantation and Organ Regeneration.
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. Both contributed to the development of the porcine thymus and kidney concept aimed at reducing the amount of immunosuppression. This surgery was the first attempt to transplant a thymic kidney from a pig into a human.
NYU Langone Health has provided financial support for the UThymoKidney and xenotransplant research initiatives and this procedure to United Therapeutics Corporation, and Apellis Pharmaceuticals, Inc., which provided Empaveli, also known as pegcetacoplan. Thank you for supporting the Compassionate Use Program. Used in off-label treatment to prevent organ rejection.
Advances in xenotransplantation
This complex intervention was carried out by the New York University Langone Transplant Institute, which has spent much of its career researching innovative approaches to expanding organ supply and performed the world's first gene-edited pig-to-human transplant surgery. This will be the sixth human xenotransplant surgery directed by Dr. Montgomery. September 25, 2021 Human organ transplantation to a neurologically deceased person with a beating heart. The same gene-edited pig kidney and thymus were used in that surgery and a second similar surgery on November 22, 2021. Surgeons at New York University Langone then performed two gene-edited pig heart transplants in the summer of 2022. A day case study of gene-edited pig kidney xenotransplants in recently deceased men showed optimal performance with standard-of-care immunosuppression.
New York University's Langone Transplant Institute has performed more xenotransplant surgeries in humans than any other institution. But before this latest surgery, gene-edited pig organs were first tested in recently deceased people to study their efficacy and viability in humans before being transplanted into living people. , five surgeries were performed using special protocols in collaboration with the families.
“This moment of transplantation would not have been possible without the generosity and altruism of those who participated in our series of fatal modeling studies,” Dr. Montgomery said. “We look forward to the opportunity to participate in clinical trials under the guidance of the FDA, and we do not have much time left to learn more about the potential for new sustainable organ sources for all.” continue.”
About New York University Langone Transplant Institute
New York University Langone Transplant Institute offers the highest quality kidney and lung transplant programs in the nation, according to high-quality federal data, but the heart and liver transplant programs have lower survival rates and waiting lists nationwide. outstanding in its success in removing patients from. In 2023, the institute conducted 576 organ transplants. NYU Langone's Heart, Kidney, Liver, Lung, and Pancreas Transplant Program is approved by the Centers for Medicare and Medicaid Services (CMS) and meets the rigorous quantity, process, quality, and survival outcome requirements of CMS regulations. means fulfilled.
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