• US surgeons transplanted a heart from a genetically modified pig into a 57-year-old man, a medical first that could one day help solve the chronic shortage of organ donations.
• While the patient’s prognosis is far from certain, it represents a major milestone for animal to human transplantation.
• 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.
Special authorisation from FDA
• 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.
• The patient, David Bennett, a Maryland resident, had been deemed ineligible for a conventional heart transplant at University of Maryland Medical Center (UMMC) as well as at several other leading transplant centers that reviewed his medical records.
• The US Food and Drug Administration (FDA) granted emergency authorisation 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 authorisation to proceed was granted in the hope of saving the patient’s life.
Tackling issues of xenotransplantation
• Xenotransplants, transplanting animal organs, 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.
• Revivicor, a regenerative medicine company based in Blacksburg, Virginia, provided the genetically-modified pig to the xenotransplantation laboratory at UMSOM.
• 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.
• The work was funded in part with a $15.7 million research grant to evaluate Revivicor’s genetically-modified pig hearts in baboon studies.
• Considered one of the world’s foremost experts on transplanting animal organs, Dr.Muhammad M. Mohiuddin, joined the UMSOM faculty five years ago and established the Cardiac Xenotransplantation Program with Dr.Bartley P. Griffith.
• 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.
• Pigs have long been a tantalizing source of potential transplants because their organs are so similar to humans. A hog heart at the time of slaughter, for example, is about the size of an adult human heart. Other organs from pigs being researched for transplantation into humans include kidneys, liver and lungs.
• 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.
• The team 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 way ahead
• “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,” Dr. Griffith, who surgically transplanted the pig heart into the patient, said.
• 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.
• 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 official figures.
• To meet demand, doctors have long been interested in so-called xenotransplantation, or cross-species organ donation.