In a first-of-its-kind surgery, a 57-year-old patient with terminal heart disease received a successful transplant of a genetically modified pig heart and is still doing well three days later. It was the only currently available option for the patient. The historic surgery was conducted by University of Maryland School of Medicine (UMSOM) faculty at the University of Maryland Medical Center (UMMC), together known as the University of Maryland Medicine. Bartley P. Griffith, MD, surgically transplanted the pig heart into the patient.

Today, Dr. Griffith is the Thomas E. and Alice Marie Hales Distinguished Professor in Transplant Surgery at UMSOM and Director of the Cardiac Transplant Program at UMMC. Prior to this appointment, Dr. Griffith served as the chief of cardiothoracic surgery at the University of Pittsburgh School of Medicine (UPMC). He was also the founder of The McGowan Center for Artificial Organ Development which was established in 1992 from a $1 million donation from William G. McGowan, founder and chairman of MCI Communications. The McGowan Institute for Regenerative Medicine was formed in 2001 by consolidating the artificial organ and medical device research of the faculty affiliated with the McGowan Center with research related to tissue engineering and cell-based therapies. The McGowan Institute works on tissue and organ insufficiency through tissue engineering, cell-based therapies, and medical devices and artificial organs, with an emphasis on translating the research findings of McGowan Institute affiliated faculty into clinical use.

This organ transplant demonstrated for the first time that a genetically modified animal heart can function like a human heart without immediate rejection by the body. The patient, David Bennett, a Maryland resident, is being carefully monitored over the next days and weeks to determine whether the transplant provides lifesaving benefits. He had been deemed ineligible for a conventional heart transplant at UMMC as well as at several other leading transplant centers that reviewed his medical records.

“It was either die or do this transplant. I want to live. I know it’s a shot in the dark, but it’s my last choice,” said Mr. Bennett, the patient, a day before the surgery was conducted. He had been hospitalized and bedridden for the past few months. “I look forward to getting out of bed after I recover.”

The U.S. Food and Drug Administration granted emergency authorization for the surgery on New Year’s Eve through its expanded access (compassionate use) provision. It 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 authorization to proceed was granted in the hope of saving the patient’s life.

“This was a breakthrough surgery and brings us one step closer to solving the organ shortage crisis. There are simply not enough donor human hearts available to meet the long list of potential recipients,” said Dr. Griffith. “We are proceeding cautiously, but we are also optimistic that this first-in-the-world surgery will provide an important new option for patients in the future.”

Considered one of the world’s foremost experts on transplanting animal organs, known as xenotransplantation, Muhammad M. Mohiuddin, MD, Professor of Surgery at UMSOM, joined the UMSOM faculty five years ago and established the Cardiac Xenotransplantation Program with Dr. Griffith. Dr. Mohiuddin serves as the program’s Scientific/Program Director and Dr. Griffith as its Clinical Director.

“This is the culmination of years of highly complicated research to hone this technique in animals with survival times that have reached beyond nine months. The FDA used our data and data on the experimental pig to authorize the transplant in an end-stage heart disease patient who had no other treatment options,” said Dr. Mohiuddin. “The successful procedure provided valuable information to help the medical community improve this potentially life-saving method in future patients.”

About 110,000 Americans are currently waiting for an organ transplant, and more than 6,000 patients die each year before getting one, according to the federal government’s Xenotransplantation could potentially save thousands of lives but does carry a unique set of risks, including the possibility of triggering a dangerous immune response. These responses can trigger an immediate rejection of the organ with a potentially deadly outcome to the patient.

Before consenting to receive the transplant, Mr. Bennett, the patient, was fully informed of the procedure’s risks, and that the procedure was experimental with unknown risks and benefits. He had been admitted to the hospital more than six weeks earlier with life-threatening arrhythmia and was connected to a heart-lung bypass machine, called extracorporeal membrane oxygenation (ECMO), to remain alive. In addition to not qualifying to be on the transplant list, he was also deemed ineligible for an artificial heart pump due to his arrhythmia.

Revivicor, a regenerative medicine company based in Blacksburg, VA, provided the genetically modified pig to the xenotransplantation laboratory at UMSOM. 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, perfusion device, a machine that keeps the heart preserved until surgery. McGowan Institute for Regenerative Medicine affiliated faculty member David Kaczorowski, MD, Surgical Director of the Advanced Heart Failure Center of UPMC Heart and Vascular Institute and an Associate Professor of Cardiothoracic Surgery, Department of Cardiothoracic Surgery, University of Pittsburgh, was a member of this landmark surgical transplant team. Previously, he worked at the University of Maryland with Dr. Griffith and Dr. Mohiuddin to perfect the pig-to-baboon heart transplants.

“This is an important step forward in medicine,” said Dr. Kaczorowski, who helped procure the heart from the donor pig. While it will likely be several years before pig organs are routinely used in humans, he said, this is a huge step in that direction. “This is the medical equivalent of landing on the moon,” he said.

The physician-scientists also used a new drug along with conventional anti-rejection drugs, which are designed to suppress the immune system and prevent the body from rejecting the foreign organ. The new drug used is an experimental compound made by Kiniksa Pharmaceuticals.

Organs from genetically modified pigs have been the focus of much of the research in xenotransplantation, in part because of physiologic similarities between pigs, human, and nonhuman primates. UMSOM received $15.7 million sponsored research grant to evaluate Revivicor genetically modified pig UHearts™ in baboon studies.

Three genes—responsible for rapid antibody-mediated rejection of pig organs by humans—were “knocked out” in the donor pig. Six human genes responsible for immune acceptance of the pig heart were inserted into the genome. Lastly, one additional gene in the pig was knocked out to prevent excessive growth of the pig heart tissue, which totaled 10 unique gene edits made in the donor pig.

Illustration:  McGowan Institute for Regenerative Medicine (Kaczorowski)/University of Maryland Medical Center (Griffith/Mohiuddin)

Read more…

University of Maryland Medical Center News Release

Pittsburgh Post-Gazette