In addition to organ rejection, infection is one of the most common complications of transplants. Doctors must strike a balance when prescribing immunosuppressants: too low a dose can lead to rejection, while too high a dose can leave a patient vulnerable to infections. Immunosuppressants are powerful medications that can cause a range of side effects, including fatigue, nausea and vomiting.
Despite the deaths of the two pig heart recipients, Riella is optimistic about Slayman’s transplant. First, he says, Slayman was relatively healthy when he underwent the surgery. He qualified for a human kidney, but because of his rare blood type he would likely have to wait six to seven years before receiving one. The two people who received a pig heart transplant were so sick that they were not eligible for a human organ.
In addition to close monitoring and traditional immunosuppressants, Slayman’s medical team is treating him with an experimental drug called tegoprubart, developed by Eledon Pharmaceuticals of Irvine, California. Tegoprubart is given by infusion every three weeks and blocks cross-talk between two important immune cells in the body, T cells and B cells, suppressing the immune response against the donor organ. The drug has been used in monkeys that have been given genetically modified pig organs.
Photo: Massachusetts General Hospital
“It’s quite miraculous that this man is allowed to leave the hospital just a few weeks after having a pig kidney implant,” said Steven Perrin, Eledon’s president and chief scientific officer. “I didn’t think we would get here as quickly as we did.”
Riella is also hopeful that the 69 genetic changes made to the pig that provided the donor organ will keep Slayman’s kidneys functioning. Pig organs are naturally incompatible in the human body. The company that supplied the pig, eGenesis, used Crispr to add certain human genes, remove some pig genes, and inactivate latent viruses in the pig genome that could hypothetically infect a human recipient. The pigs are produced through cloning; Scientists edit a single pig cell and use that cell to form an embryo. The embryos are cloned and placed back into the uterus of a female pig so that her offspring can be included in the operations.
“We hope this combination will be the secret sauce to ensuring this kidney has longer graft survival,” says Riella.
There is debate among scientists about how much processing pig organs require in humans. For the pig heart transplants, researchers used donor animals with 10 operations, developed by United Therapeutics subsidiary Revivicor.
There’s another big difference between this procedure and the heart surgeries: If Slayman’s kidney were to stop working, Riella says, he could resume dialysis. The pig heart recipients had no backup options. He says that even if pig organs are not a long-term alternative, they could provide a bridge to transplantation for patients like Slayman who would otherwise have to spend years on dialysis.
“We have received so many letters, emails and messages from people who voluntarily wanted to apply for the xenotransplants, despite all the uncertainties,” says Riella. “Many of them have so much difficulty with dialysis that they are looking for an alternative.”
The Mass General team plans to launch a formal clinical trial to transplant edited pig kidneys into more patients. They received special approval from the U.S. Food and Drug Administration for only one procedure. For now, however, their main focus is on keeping Slayman healthy.