On September 20, a 58-year-old patient with fatal heart disease became the world’s second recipient of a historic transplant of a genetically-modified pig heart. He is healing and interacting with his family. This is only the second time a genetically engineered pig heart has been transplanted into a living patient in the world. Both landmark surgeries were carried out by faculty from the University of Maryland School of Medicine (UMSOM) at the University of Maryland Medical Center (UMMC).
The first historic surgery was done on David Bennett in January 2022 by University of Maryland Medicine surgeons (UMSOM and UMMC), who are renowned as the pioneers in cardiac xenotransplantation. Lawrence Faucette, the new patient, had advanced heart disease. Due to his pre-existing peripheral vascular disease and difficulties with internal bleeding, UMMC and several other premier transplant institutions judged him ineligible for a typical human heart transplant.
Mr. Faucette was facing near-certain death from cardiac failure, and this transplant was his final chance. The patient, a married father of two from Frederick, MD, is a 20-year Navy veteran who most recently worked as a lab technician at the National Institutes of Health before retiring. He is currently breathing on his own and his heart is beating normally without the use of any assistive equipment.
“My only real hope left is to go with the pig heart, the xenotransplant,” said Mr. Faucette during an interview from his hospital room a few days before his surgery. “Dr. Griffith, Dr. Mohiuddin and their entire staff have been incredible, but nobody knows from this point forward. At least now I have hope, and I have a chance.”
Added his wife, Ann Faucette: “We have no expectations other than hoping for more time together. That could be as simple as sitting on the front 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. This approval process is used when an experimental medical product, in this case the genetically-modified pig’s heart, is the only option available for a patient faced with a serious or life-threatening medical condition. The approval was granted in the hope of saving the patient’s life.
“We are once again offering a dying patient a shot at a longer life, and we are incredibly grateful to Mr. Faucette for his bravery and willingness to help advance our knowledge of this field,” said 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 and Clinical Director of the Cardiac Xenotransplantation Program at UMSOM. “We are hopeful that he will get home soon to enjoy more time with his wife and the rest of his loving family.”
Muhammad M. Mohiuddin, MD, Professor of Surgery at UMSOM, is widely regarded as one of the world’s best experts on xenotransplantation. He joined the UMSOM faculty seven years ago and developed the Cardiac Xenotransplantation Program. Dr. Mohiuddin is the Program/Scientific Director of the program. Dr. Mohiuddin and Dr. Griffith co-led this procedure.
“We are continuing to pursue the pathway to clinical trials by providing important new data on pre-clinical research that has been requested by the FDA,” 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 an end-stage heart disease patient who had no other treatment options.”
According to the federal government’s organdonor.gov, over 110,000 Americans are now on the waiting list for an organ transplant, and more than 6,000 patients die each year before receiving one. Transplanting animal organs (also known as xenotransplantation) has the potential to save millions human lives, but it comes with its own set of concerns. Aside from the concern about spreading an unknown infection from animal to human, xenotransplants are more likely to elicit a severe immunological reaction. These reactions can result in an abrupt rejection of the organ, which might be fatal to the patient.
“As a cardiothoracic surgeon who does lung transplants, I am so grateful to our team of surgeons who are working to help solve the organ shortage crisis,” said Christine Lau, MD, MBA the Dr. Robert W. Buxton Professor and Chair of the Department of Surgery at UMSOM and Surgeon-in-Chief at UMMC. “Once again, we are at the forefront of a historic accomplishment that brings us one step closer to making xenotransplantation a life-saving reality for patients in need.”
United Therapeutics Corporation, situated in Blacksburg, Virginia, gave the genetically engineered pig to the UMSOM xenotransplantation laboratory through its xenotransplantation subsidiary Revivicor. The surgical team, led by Drs. Griffith and Mohiuddin, withdrew the pig’s heart and placed it in the XVIVO Heart Box, a machine perfusion device, to maintain the heart preserved until surgery.
In addition to conventional anti-rejection medications that suppress the immune system and prevent the body from destroying or rejecting the foreign organ, the physician-scientists are treating the patient with a new antibody therapy. Eledon Pharmaceuticals is developing a novel medication called tegoprubart, which is an investigational antibody that suppresses CD154, a protein implicated in immune system activation.
Mr. Faucette was fully advised of the surgery’s hazards prior to consenting to have the transplant, as well as the fact that the procedure was experimental with uncertain risks and benefits. On Thursday, September 14, he was taken to UMMC due to complications from his heart failure and peripheral vascular disease. Mr. Faucette had a psychiatric evaluation and met with a medical ethicist, social workers, and other members of the UMMC care team to explain the risks and advantages of the treatment and acquire his informed consent.
“This innovative program embodies the future of molecular medicine in surgery and speaks to a possible future where organs may be available to all patients,” said UMSOM Dean Mark Gladwin MD, who is also Executive Vice President for Medical Affairs, 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 transplantation medicine into the next era. I appreciate the hard work of so many of our clinical, research and administrative teams at the University of Maryland Medicine. They have worked so hard over the last year to prepare for this day, doing everything possible to optimize the outcome of this historic surgery.”
“This transplant is another remarkable achievement for medicine and humanity that would not have been possible without the close relationship between University of Maryland Medical Center and our University of Maryland School of Medicine partners,” 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 are pressing onward to propel the xenotransplantation field forward. We are immensely proud to have taken another significant leap toward a day when more people who need a lifesaving organ transplant can get one.”
“This is an exciting time for everyone in the xenotransplantation field,” said Mohan Suntha, MD, MBA, University of Maryland Medical System President and CEO. “We’ve seen an astonishing amount of progress in a short period of time and our System is proud to be part of this incredible milestone. This is the result of the resolve and tenacity of researchers who have held fast to the vision over decades. Those team members who have been directly involved in this work as well as those who have watched in hopeful interest are each part of a medical community that can feel the magnitude of this moment.”
Much of the research on xenotransplantation has focused on organs from genetically modified pigs, owing to physiologic similarities between pigs and human and nonhuman primates. United Therapeutics has funded a $22 million research initiative at UMSOM to test their Revivicor genetically modified pig hearts in baboon trials.
Three genes, which are responsible for human antibody-mediated rejection of pig organs, were “knocked out” in the donor pig. Six human genes essential for pig heart immune acceptance were introduced into the genome. One more gene was knocked out in the pig to avoid excessive growth of the pig heart tissue, for a total of ten distinct gene edits in the donor pig.
“This procedure is another significant step forward in bringing our vision of lifesaving xenotransplantation to those patients in desperate need,” said David Ayares, PhD, President and Chief Scientific Officer of United Therapeutics Corporation’s Revivicor subsidiary. “This second successful transplantation of United Therapeutics’ UHeart™ is a product of decades of gene editing, animal husbandry, and creative thinking by the team of scientists at United Therapeutics and Revivicor, and at the University of Maryland—especially Drs. Mohiuddin and Griffith. All of us at United Therapeutics recognize the bravery and unconditional willingness by Mr. Faucette to advance the cause of science and medical treatment in this remarkable way.”
UMSOM faculty-scientists have thoroughly researched Mr. Bennett’s experience with the world’s first genetically engineered cardiac xenotransplant in the nearly two years since the original surgery. They first published their findings in the New England Journal of Medicine, and then in The Lancet, they reported their follow-up findings after an extended examination. They showed that the pig heart worked properly in the patient for several weeks with no evidence of severe rejection. Mr. Bennett’s death from heart failure was most likely caused by a combination of conditions, including his poor health, which had him hospitalized for six weeks prior to the transplant on a heart-lung bypass system.
Dr. Mohiuddin, Dr. Griffith, and their research team spent five years honing the surgical method on non-human primates before executing the first surgery on Mr. Bennett in 2022. Dr. Mohiuddin has over 30 years of xenotransplant research expertise, during which time he established in peer-reviewed study that a genetically engineered pig’s heart can function when placed in the abdomen for up to three years.
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