In addition to organ rejection, one of the most common transplant complications is infection. Doctors must strike a balance when prescribing immunosuppressive drugs: too low a dose can cause rejection, while too much can leave the patient vulnerable to infection. Immunosuppressants are powerful drugs that can cause a range of side effects, including fatigue, nausea and vomiting.
Despite the deaths of two pig heart recipients, Riera is optimistic about Slyman’s transplant. For one thing, Slimane was relatively healthy when he underwent surgery, he said. He is eligible for a human kidney, but because of his rare blood type, he may have to wait six to seven years to get one. Two people who received pig heart transplants were seriously ill and ineligible to receive human organs.
In addition to close monitoring and traditional immunosuppressants, Slimane’s medical team is treating him with an experimental drug called tegoprubart, developed by Eledon Pharmaceuticals of Irvine, Calif. Infused intravenously every three weeks, tegoprubart blocks crosstalk between two key immune cells in the body: T cells and B cells, which helps suppress the immune response against the donor organ. The drug has been used in monkeys that received organs from gene-edited pigs.
Photo: Massachusetts General Hospital
“It’s miraculous that this guy was discharged from the hospital just a few weeks after the pig kidney was implanted,” said Steven Perrin, president and chief scientific officer of Eledon. “I didn’t think we’d be here so quickly. “
Riella also hopes that 69 genetic modifications made to the pigs that provided the donor organs will help Slayman’s kidneys keep functioning. Pig organs are not naturally compatible in humans. eGenesis, a company that supplies pigs, uses Crispr to add certain human genes, delete some pig genes, and inactivate latent viruses in the pig genome that might infect human recipients. The pigs are produced through cloning technology; scientists edit a single pig cell and use that cell to form an embryo. The embryos are cloned and transferred into the sow’s uterus so that her offspring can eventually be edited.
“We hope this combination will be the secret to longer survival of transplanted kidneys,” Riella said.
Scientists debate how many times pig organs need to be edited before they can persist in humans. In the pig heart transplant, the researchers used 10-edited donor animals developed by United Therapeutics subsidiary Revivicor.
There’s another big difference between this surgery and heart surgery: Riera says that if Slimane’s kidneys do stop working, he can resume dialysis. There is no backup option for pig heart recipients. Even if pig organs aren’t a long-term replacement, he said, they could provide a bridge to transplant for patients like Slimane who would otherwise spend years on dialysis.
“We received a lot of letters, emails and messages from people who volunteered to be xenotransplant candidates, even though everything was unknown,” Riera said. “Many of them are struggling with dialysis to the point where they are looking for alternatives.”
The MGH team plans to launch a formal clinical trial to transplant the edited pig kidneys into more patients. They have only received specific approval for one procedure from the U.S. Food and Drug Administration. For now, though, their main focus is keeping Slayman healthy.