Successful transplant of porcine heart into adult human with end-stage
heart disease
First-of-its-kind transplant was patient's only option for survival after being deemed ineligible for traditional transplant

Date:
January 10, 2022
Source:
University of Maryland School of Medicine
Summary:
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.



FULL STORY ==========================================================================
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.


==========================================================================
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 Bartley
P. Griffith, MD, who surgically transplanted the pig heart into the
patient. Dr. Griffith is the Thomas E. and Alice Marie Hales Distinguished Professor in Transplant Surgery at UMSOM. "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 organdonor.gov. 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.

Xenotransplants were first tried in the 1980s, but were largely abandoned
after the famous case of Stephanie Fae Beauclair (known as Baby Fae)
at Loma Linda University in California. The infant, born with a fatal
heart condition, received a baboon heart transplant and died within
a month of the procedure due to the immune system's rejection of the
foreign heart. However, for many years, pig heart valves have been used successfully for replacing valves in humans.

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 arrythmia
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.



==========================================================================
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.

"This unprecedented and historic procedure highlights the importance of translational research which lays the groundwork for patients to benefit
in the future. It is the culmination of our longstanding commitment
to discovery and innovation in our xenotransplantation program," said
E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical
Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. "Our
transplant surgeon-scientists are among the most talented in the
country, and are helping to bring the promise of xenotransplantation to fruition. We hope it will one day become a standard of care for patients
in need of organ transplants. As has happened throughout our history, the University of Maryland School of Medicine continues to address the most
complex medical and scientific problems." Bruce Jarrell, MD, President
of the University of Maryland, Baltimore, who himself is a transplant
surgeon, recalled: "Dr. Griffith and I began as organ transplant
surgeons when it was in its infancy. Back then, it was the dream of every transplant surgeon, myself included, to achieve xenotransplantation and it
is now personally gratifying to me to see this long-sought goal clearly
in view. It is a spectacular achievement." "This is truly a historic, monumental step forward. While we have long been at the forefront of
research driving progress toward the promise of xenotransplantation as
a viable solution to the organ crisis, many believed this breakthrough
would be well into the future," said Bert W. O'Malley, MD, President and
CEO, University of Maryland Medical Center. "I couldn't be more proud
to say the future is now. Our skilled team of UMMC and UMSOM physician- scientists will continue to advance and adapt medical discovery for
patient care that could offer a lifeline for more patients in dire need."
Mohan Suntha, MD, MBA, President and CEO, University of Maryland Medical System, added: "The University of Maryland Medical System is committed
to working with our University of Maryland School of Medicine partners to explore, research, and in many cases implement the innovations in patient
care that make it possible to improve quality of life and save lives. We appreciate the tremendous courage of this live recipient, who has made an extraordinary decision to participate in this groundbreaking procedure
to not only potentially extend his own life, but also for the future
benefit of others." 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 [TM] 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.

"We are thrilled to support the world-class team of transplant surgeons
led by Dr. Griffith and Dr. Mohiuddin at the University of Maryland
School of Medicine," said David Ayares, PhD, Chief Scientific Officer
of Revivicor, Inc.

"This transplant is groundbreaking, and is another step in the
investigation of xeno organs for human use." Dr. Mohiuddin, Dr. Griffith,
and their research team spent the past five years perfecting the
surgical technique for transplantation of pig hearts into non- human
primates. Dr. Mohiuddin's xenotransplant research experience spans over
30 years during which time he demonstrated in peer-reviewed research that genetically-modified pig's hearts can function when placed in the abdomen
for as long as three years. Success was dependent on the right combination
of genetic modifications to the experimental donor pig UHeart[TM] and
anti- rejection drugs, including some experimental compounds.

"As a cardiothoracic surgeon who does lung transplants, this is an
amazing moment in the history of our field. Decades of research here at Maryland and elsewhere have gone into this achievement. This has the
potential to revolutionize the field of transplantation by eventually eliminating 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. "This is a continuation of steps to
making xenotransplantation a life- saving reality for patients in need."
Daniel G Maluf, MD, FAST, Professor of Surgery and Medicine at UMSOM
and Director, UMSOM's Program in Transplantation, added: "This is a breakthrough for the field of organ transplantation and medicine,"
he said. "This event is the final achievement of years of research
and testing from our multidisciplinary team led by Dr. Griffith
and Dr. Mohiuddin and represents a beginning of a new era in the
field of organ transplantation medicine. I am proud of our team's
incredible achievement." Peter Rock, MD, MBA, the Dr. Martin Helrich
Chair and Professor in the Department of Anesthesiology at UMSOM,
said: "We carefully considered the unique needs of this patient in
preparing him for surgery and the intricacies involved in modifying our anesthetic techniques for this xenotransplant procedure. Our planning
paid off, and the surgery could not have gone better thanks to the
herculean efforts of the medical team involved in this landmark event." ========================================================================== Story Source: Materials provided by
University_of_Maryland_School_of_Medicine. Original written by Deborah
Kotz. Note: Content may be edited for style and length.


========================================================================== Related Multimedia:
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YouTube_video:_First_Ever_Pig_to_Human_Heart_Transplant_(University_of
Maryland_Medicine) ==========================================================================


Link to news story: https://www.sciencedaily.com/releases/2022/01/220110183051.htm
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