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. Strong medications 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 too sick to qualify for 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. Administered via intravenous injection every three weeks, tegoprubart blocks crosstalk between two key immune cells in the body, T cells and B cells, helping to suppress immune responses against donated organs. 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, Eledon’s president and chief scientific officer. “I had no idea we would be here so quickly.”
Riella also hopes that 69 genetic modifications made to the pigs that provided the donated organs will help Sleiman’s kidneys keep functioning. Pig organs are not naturally compatible in humans. The company that provides the pigs, eGenesis, uses Crispr to supplement certain human genes, delete some pig genes, and inactivate latent viruses in the pig genome that might infect human recipients. The pigs were created through cloning; scientists edited a single pig cell and used 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 are no backup options for pig heart recipients. Even if pig organs aren’t long-term — as a long-term alternative — they could provide a bridge to transplant for patients like Slayman who would otherwise spend years on dialysis, he said.
“We’ve received a lot of letters, emails and messages from people who have volunteered to be xenotransplant candidates, even though everything is still unknown,” Riera said. “
The team at Massachusetts General Hospital plans to launch a formal clinical trial to transplant gene-edited pig kidneys into more patients. They received special approval from the U.S. Food and Drug Administration for just one procedure. For now, though, their main focus is keeping Slayman healthy.
