Second historic pig heart transplant A 58-year-old patient with terminal heart disease became the second patient in the world on September 20 to successfully receive a genetically modified pig heart transplant . He recovers well and communicates with his loved ones. This is only the second time in the world that a genetically modified pig heart has been transplanted into a living patient. Both landmark surgeries were performed by University of Maryland School of Medicine (UMSOM) faculty at the University of Maryland Medical Center (UMMC).
The historic first surgery, performed in January 2022, was performed on David Bennett by University of Maryland Medicine surgeons (comprising UMSOM and UMMC), who are recognized as leaders in cardiac xenotransplantation. This new patient, Lawrence Faucette, had a terminal heart condition. UMMC and several other leading transplant hospitals deemed him 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 to Mr. Faucette, who faced almost certain death from heart failure. The patient, who lives in Frederick, MD, is married, a father of two, and a 20-year Navy veteran who most recently worked as a laboratory technician at the National Institutes of Health before retiring. He is currently breathing on his own and his heart is functioning well without the aid of assistive devices.
“The only real hope I have left is to opt for the pig heart, the xenotransplant,” Faucette said during an interview from his hospital room a few days before his surgery. "Dr. Griffith, Dr. Mohiuddin and his entire staff have been amazing, but no one knows as of right now. At least now I have hope and I have a chance."
His wife, Ann Faucette, added: “We have no expectations other than spending more time together. "That could be as simple as sitting on the porch and having coffee together."
The U.S. Food and Drug Administration granted emergency approval for the surgery on Friday, September 15, through its single-patient investigational new drug (IND) “compassionate use” pathway. The approval process is used when an experimental medical product, in this case genetically modified pig heart, is the only option available to a patient facing a serious or life-threatening medical condition. Approval was granted in hopes of saving the patient’s life.
"Once again we offer a dying patient the opportunity to live a longer life, and we are incredibly grateful to Mr. Faucette for his bravery and willingness to help us advance our knowledge of this field," said Bartley P. Griffith, MD, who surgically transplanted the pig heart to the second patient, as well as the first patient to receive this innovative surgery at UMMC. Dr. Griffith is the Thomas E. and Alice Marie Hales Distinguished Professor in Transplant Surgery and Clinical Director of the UMSOM Cardiac Xenotransplant Program. "We are hopeful that he will come home soon to enjoy more time with his wife and the rest of his loving family."
Considered one of the world’s leading experts in xenotransplantation, Muhammad M. Mohiuddin, MD, UMSOM Professor of Surgery, joined the UMSOM faculty seven years ago and established the Cardiac Xenotransplantation Program. Dr. Mohiuddin serves as the program’s scientific and program director. Dr. Mohiuddin co-led this procedure with Dr. Griffith.
"We continue to move toward clinical trials by providing important new data on the preclinical research that the FDA has requested," said Dr. Mohiuddin. "The FDA used our data from these new studies, as well as our experience with the first patient, to determine that we were ready to attempt a second transplant in a patient with end-stage heart disease who had no other treatment options."
About 110,000 Americans are currently waiting for an organ transplant, and more than 6,000 patients die each year before receiving one, according to the federal government’s organdonor.gov. Transplanting animal organs (known as xenotransplantation ) could save thousands of lives, but it carries a unique set of risks. In addition to the fear of transmitting an unknown pathogen from the animal to the human, xenotransplantations are more likely to trigger a dangerous immune response. These responses can trigger immediate rejection of the organ with a potentially fatal outcome for the patient.
"As a cardiothoracic surgeon who performs lung transplants, I am very grateful to our team of surgeons who are working to help solve the organ shortage crisis," said Christine Lau, MD, MBA. Dr. Robert W. Buxton, Professor and chairman of the UMSOM Department of Surgery and chief surgeon at UMMC. "Once again, we are at the forefront of a historic achievement that brings us one step closer to making xenotransplantation a life-saving reality for patients in need."
United Therapeutics Corporation , through its xenotransplantation subsidiary Revivicor, based in Blacksburg, VA, provided the genetically modified pig to the UMSOM xenotransplantation laboratory. On the morning of the transplant surgery, the surgical team, led by Dr. Griffith and Dr. Mohiuddin, removed the pig’s heart and placed it in the XVIVO Heart Box, an automated perfusion device, to keep the heart preserved. until surgery.
Doctors also treat the patient with a new antibody therapy along with conventional anti-rejection medications, which are designed to suppress the immune system and prevent the body from damaging or rejecting the foreign organ. The new therapy being developed by Eledon Pharmaceuticals is an experimental antibody, called tegoprubart; blocks CD154, a protein involved in activating the immune system.
Before consenting to receive the transplant, Mr. Faucette was fully informed of the risks of the procedure and that the procedure was experimental and the risks and benefits were unknown. He was admitted to UMMC on Thursday, September 14 after experiencing complications from his heart failure and peripheral vascular disease. Mr. Faucette underwent a psychiatric evaluation and met with a medical ethicist, social workers, and other members of the UMMC care team to discuss the risks and benefits of the procedure and obtain informed consent from him.
"This innovative program embodies the future of molecular medicine in surgery and speaks to a possible future in which organs can be available to all patients," said UMSOM Dean Mark Gladwin, MD, who is also executive vice president. of Medical Affairs at UM Baltimore and the John Z. and Akiko K. Bowers Distinguished Professor at UMSOM. “We recognize a heroic partnership with Mr. Faucette and his family as we partner to advance the field of transplant medicine into the next era. I appreciate the hard work of many of our clinical, research, and administrative teams at the Medical University of Maryland. “They have worked very hard over the past year to prepare for this day, doing everything they can to optimize the outcome of this historic surgery.”
The surgical team at the University of Maryland Medicine showed that the pig heart worked well in Mr. Faucette and showed no signs of hyperacute immunological rejection. He will be closely monitored for evidence of porcine infections. Before transplantation, the donor pig was routinely tested for multiple porcine viruses, bacteria, and parasites, and the tests did not reveal any unexpected pathogens. The next few weeks will be crucial in determining whether Mr. Faucette’s body continues to tolerate the transplanted pig organ without any signs of life-threatening immune system rejection.
"This transplant is another remarkable achievement for medicine and humanity that would not have been possible without the close relationship between the University of Maryland Medical Center and our partners at the University of Maryland School of Medicine," said Bert W. O’Malley, MD, president and CEO of the University of Maryland Medical Center. “The Faucettes and thousands of families like them are the reason we continue to advance the field of xenotransplantation. “We are immensely proud to have taken another significant leap towards the day when more people who need a life-saving organ transplant can receive one.”
"This is an exciting time for everyone in the xenotransplantation field," said Mohan Suntha, MD, MBA, President and CEO of the University of Maryland Medical System. “We have seen an amazing amount of progress in a short period of time and our system is proud to be a part of this incredible milestone. This is the result of the determination and tenacity of researchers who have held onto this vision for decades. “The team members who have been directly involved in this work, as well as those who have watched with hopeful interest, are part of a medical community that can feel the magnitude of this moment.”
Organs from genetically modified pigs have been the focus of much xenotransplantation research, in part because of the physiological similarities between pigs and human and non-human primates. United Therapeutics has funded a $22 million research program to test its genetically modified pig hearts from Revivicor in baboon studies conducted at UMSOM.
Three genes, responsible for the rapid antibody-mediated rejection of pig organs by humans, were “knocked out” in the donor pig. Six human genes responsible for the immune acceptance of the pig heart were inserted into the genome. An additional gene was deleted in the pig to prevent overgrowth of the pig’s heart tissue, for a total of 10 unique gene edits made to the donor pig.
"This procedure is another important step forward in bringing our vision of life-saving xenotransplantation to patients who desperately need it," said David Ayares, Ph.D., president and chief scientific officer of United Therapeutics Corporation’s Revivicor subsidiary. “This second successful UHeart™ transplant from United Therapeutics is the product of decades of gene editing, animal husbandry and creative thinking by the team of scientists at United Therapeutics and Revivicor, and the University of Maryland, especially Drs. Mohiuddin and Griffith. “All of us at United Therapeutics recognize Mr. Faucette’s bravery and staunch willingness to advance the cause of science and medical treatment in this remarkable way.”
In the nearly two years since the first surgery, UMSOM scientists and faculty have extensively researched Mr. Bennett’s experience with the world’s first genetically modified heart xenotransplantation. They published their initial findings in the New England Journal of Medicine and then published follow-up findings from extensive research in The Lancet . They showed that the pig heart worked well in the patient for several weeks with no signs of acute rejection. Mr. Bennett’s death from heart failure was likely caused by a multitude of factors, including his poor health that left him hospitalized on a heart-lung machine for six weeks before the transplant.
Before performing the first surgery on Mr. Bennett in 2022, Dr. Mohiuddin, Dr. Griffith and their research team spent five years perfecting the surgical technique in non-human primates. Dr. Mohiuddin’s xenotransplantation research experience spans more than 30 years, during which time he demonstrated in peer-reviewed research that the heart of a genetically modified pig can function when placed in the abdomen for up to three years.
