58-year-old Lawrence Faucette has become a medical milestone this month, being only the second living person in the world to have received a heart transplant from a genetically modified pig.
His doctors at the University at Maryland School of Medicine say that Faucette appears to be doing well and that his new heart is functioning as expected. However, time will tell whether the team has avoided the stumbles that might have contributed to the death of their first patient last year, David Bennett, just two months after he received his transplant.
Animal-to-human transplantation, or xenotransplantation, has been a long-sought-after goal in the transplant medicine field. Given the constant shortage of human organ donors, safe and effective xenotransplantation would likely save many lives who otherwise would die on the waiting list. The trouble is that our immune systems are already naturally hostile to donated organs and tissues from other people, and we’re even less compatible with other animals.
In recent years, however, some scientists believe that they’ve made a giant leap forward in making xenotransplantation a viable reality. By tweaking a few genes in pigs, they theorize that it’s possible to make their organs human-like enough for transplantation to work. Perhaps the most important change is the knocking out of a gene responsible for producing alpha-gal, a sugar found in the muscles of most mammals, but not humans (this same quirk is why people can rarely develop an allergy to red meat caused by the bite of certain ticks). These modified pigs have been developed by United Therapeutics Corporation, through its division Revivicor.
So far, researchers have largely relied on using brain dead patients (with the permission of their families) to test out this technology. These experiments have shown that these pig organs can avoid immediate rejection by the body and function for up to several months, and have set the stage for larger clinical trials in the near future. But researchers at UMSOM were granted permission by the Food and Drug Administration in January 2022 to perform such a transplant with 57-year-old David Bennett as an experimental treatment of last resort—a treatment that has once again been approved for Lawrence Faucette.
Like Bennett, Faucette has been diagnosed with terminal heart disease and is not considered eligible to receive a traditional heart transplant. Despite the possible risks, Faucette agreed to undergo the procedure, which took place on September 20. As of the middle of last week, his doctors say Faucette has been breathing on his own and that his new heart is working well without the need for supportive devices.
“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 Griffith, who has performed both transplants and is the clinical director of the cardiac xenotransplantation program at UMSOM, in a statement from the university. “We are hopeful that he will get home soon to enjoy more time with his wife and the rest of his loving family.”
The team notes that there are several lessons they have learned from their experiences with David Bennett, who appeared to be doing well at first but rapidly declined in health and died in March 2022.
An investigation into his death found that his new heart unknowingly carried a latent pig virus called porcine cytomegalovirus (PCMV). The virus didn’t appear to directly infect Bennett, but it may have reactivated and damaged the heart after his antiviral treatment was reduced to address other health issues. Bennett was also severely immunocompromised to begin with, which might have affected the expected success (based on animal studies) of the drug regimen he was given to avoid organ rejection. And the team gave Bennett doses of intravenous immunoglobulin to help prevent infection that might have triggered an immune response to the pig heart.
The UNSOM team and other researchers now perform a more extensive screening of latent viruses in transplanted pig organs. They’re also testing out an experimental antibody treatment designed to prevent rejection alongside conventional transplant drugs this time around. Ultimately, though, it’s still possible that Faucette’s new heart may not last long for any number of reasons.
The average five-year survival rate for heart transplant recipients nowadays is around 70%, but was much worse when the technology first emerged. And many experts believe that it will take quite some time before xenotransplantation could be expected to reach this standard. For his part, Faucette is willing to accept the unknowns.
“My only real hope left is to go with the pig heart, the xenotransplant,” said Faucette in an interview given 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.”
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