Besides organ rejection, one of the most common transplant complications is infection. Physicians must maintain a balance when prescribing immunosuppressants. Too low a dose can cause rejection, while too much can leave patients vulnerable to infection. Immunosuppressants are powerful drugs that can cause various side effects, including fatigue, nausea, and vomiting.
Despite the deaths of two pig heart recipients, Riella is optimistic about Slayman's transplant. First of all, he said Slayman was relatively healthy when he had the surgery. He was eligible for a human kidney, but because of his rare blood type, he will likely have to wait six to seven years to get one. The two people who received pig heart transplants were too sick to be eligible for human organ transplants.
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 in Irvine, California. Tegofruvart, administered via IV every three weeks, helps suppress the immune response to the donor organ by blocking crosstalk between the body's two main immune cells, T cells and B cells. The drug was used on monkeys that had been transplanted with gene-edited pig organs.
“It’s truly miraculous that this person was released from the hospital just weeks after receiving a pig kidney transplant,” said Steven Perrin, Eledon’s president and chief scientific officer. “I never thought we would be here as quickly as we are now.”
Riella also hopes that 69 genetic modifications applied to pigs from which donor organs were sourced will help maintain Slayman's kidney function. Pig organs are naturally incompatible with the human body. eGenesis, the company that supplied the pigs, used Crispr to add specific human genes, remove some pig genes, and inactivate latent viruses in the pig genome that could hypothetically infect human recipients. Pigs are produced through cloning. Scientists edit single pig cells and use those cells to form embryos. The embryos are cloned and transferred to the uterus of a female pig, where the piglets also undergo editing.
“We hope this combination will be the secret to extending transplant survival of these kidneys,” says Riella.
There is debate among scientists about how long pig organs should last in humans. In the pig heart transplant, researchers used donor animals with 10 different edits developed by Revivicor, a United Therapeutics subsidiary.
There is another big difference between this surgery and heart surgery. Once Slayman's kidneys stop functioning, Riella says, dialysis can resume. Porcine heart recipients had no backup options. Even though pig organs are not a long-term alternative, they could provide a bridge to transplant for patients like Slayman who would otherwise spend years on dialysis, she said.
“We have received many letters, emails and messages from people volunteering to be xenotransplantation candidates, even though not everything is known,” Riella said. She said, “Many people are struggling with dialysis and are looking for alternatives.”
The Mass General team plans to launch formal clinical trials to transplant the edited pig kidneys into more patients. They have received special approval from the U.S. Food and Drug Administration (FDA) for just one procedure. But for now, the focus is on keeping Slayman healthy.