Advancements in Xenotransplantation: A Pig's Heart Gives Hope to Mankind

• DNA

Scientists are pushing the boundaries of medical science, as the second-ever heart transplant from a genetically modified pig has been successfully performed. The recipient, a 58-year-old man named Lawrence Faucette, was on the brink of death due to heart failure. Traditional transplantation with a human organ was not possible in his case.

“At least now I have hope, and I have a chance,” Faucette said before undergoing the University of Maryland Medical Center procedure. The surgery has opened new doors for xenotransplantation, transplanting animal organs into humans, a potential solution for the dire organ shortage. In the United States, over 104,000 people are on the waitlist for a transplant, with around 17 individuals dying daily as they wait.

Genetically Modified Pigs: The Key to Overcoming Organ Shortage

Researchers have turned to pigs as potential donors due to the similarity in size of their organs to human organs. However, pig organs are not naturally compatible with human bodies and may trigger a fatal immune response. To overcome this, scientists have made genetic modifications to the donor pigs.

The heart that Faucette received had undergone ten genetic edits. Three genes responsible for immune rejection were eliminated, while another was deleted to reduce the risk of transmission of innate pig viruses. Additionally, six human genes that affect immune acceptance were incorporated into the pig's genome.

The Journey of Xenotransplantation and its Challenges

David Bennett was the first person to receive a genetically engineered pig heart in January 2022. For seven weeks following the transplant, Bennett demonstrated robust cardiac function without signs of acute rejection, where the immune system perceives the new organ as foreign and begins to attack it. Unfortunately, Bennett passed away two months later due to sudden heart failure. The cause was speculated to be a combination of factors, including his poor health before the transplant and the detection of a latent pig virus, porcine cytomegalovirus (PCMV), in his blood.

With every organ transplant, doctors face the challenge of preventing infections while suppressing the immune system. In Bennett’s case, doctors administered intravenous immunoglobulin to combat the CMV infection. While the treatment successfully dealt with the disease, the natural antibodies it contained likely attacked the pig organ and caused damage to the muscle cells.

A New Hope: Second Pig Heart Transplant

In the case of Faucette, the Maryland doctors are taking additional steps to prevent the new heart from being rejected. They have developed a more sensitive test to detect tiny amounts of pig virus DNA. Before the transplant, the donor pig was regularly tested for CMV and other pig viruses, bacteria, and parasites.

Additionally, Faucette is being treated with traditional immunosuppressive drugs, supplemented with an investigational antibody therapy called tegoprubart. Developed by California-based biotech company Eledon Pharmaceuticals, this drug works by blocking CD154, a protein involved in immune rejection. Faucette will need to receive this treatment for the rest of his life to prevent his new heart from being rejected.

The next few weeks will be crucial to understanding whether the transplanted pig heart will continue functioning normally. Researchers are optimistic that the lessons learned from Bennett's case will improve subsequent patients' survival odds. The progress made in these individual cases of pig-to-human transplants is paving the way for more formal clinical trials.

As we stand on the precipice of a new era in organ transplantation, these experimental surgeries offer hope to those waiting for a life-saving organ. The journey is still fraught with challenges, but each step forward brings us closer to a future where the organ shortage is a thing of the past.