Trial in US offers hope for solving organ shortage

Patient Tim Andrews about to receive a genetically engineered pig kidney transplant © Kate Flock/Massachusetts General Hospital

Organs grown in animals for use in humans are beginning to build up a record of clinical success after decades of unfulfilled promise, offering hope for the future of transplants.

Five patients at Massachusetts General Hospital in the US have undergone successful transplants with animal organs — a process known as xenotransplantation — since March 2024 after the pig kidneys they received were genetically engineered to avoid rejection, US biotech company eGenesis said. In three of them, the porcine organs worked for more than eight months without rejection or the need for dialysis.

“The organ shortage is the greatest crisis we have right now in transplantation,” said Leonardo Riella, director of kidney transplantation at Mass General, who led the eGenesis clinical trials.

“It’s amazing to see the progress,” said Mike Curtis, chief executive of eGenesis. “Our goal is to make transplantation available to patients when they need it, without being constrained by the limited supply of human donor organs.”

The animal organs would initially be used “as a bridge to get patients off dialysis while they wait for a human donor kidney,” said Riella, adding that it could eventually be used “as a destination therapy in its own right” if the trials “establish long-term safety and durability”.

The kidneys were grown in Yucatan miniature pigs whose organs are similar in size to their human counterparts. They were genetically engineered to remove three pig proteins that are most likely to lead to immune rejection and add seven human genes to improve compatibility with the patient. In addition, the porcine DNA was manipulated to inactivate viruses that might infect the recipient.

One patient, Tim Andrews, whose case was described in The Lancet journal on Thursday, lived with a pig kidney, which he received aged 66, for almost nine months without needing dialysis until the transplanted organ began to fail, though there were no signs of immune rejection. He then received a kidney from a deceased human donor. Subsequent tests showed that living with the pig kidney had not made it harder for the human transplant to work successfully.

Tim Andrews leaves Massachusetts General Hospital a week after his xenotransplant operation © Kate Flock/Massachusetts General Hospital

Curtis said the US Food and Drug Administration had authorised an expanded clinical trial of eGenesis pig kidneys in 33 patients with renal failure to start early next year in up to 10 US transplant centres, with the aim of achieving marketing approval by the end of 2029. The company is also collaborating with a Japanese partner, PorMedTec, to start kidney xenografts in Japan in 2028, he added.

David Crosby, chief research officer at the renal charity Kidney Research UK, said the breakthrough was “an exciting prospect” but he warned that further research was needed to determine whether the approach was “safer and better” for patients than spending years on dialysis while they waited for a transplant.

Xenotransplantation has been through cycles of hope and disappointment since serious research on the area started in the 1980s. But recent progress in animal cloning, genetic manipulation and immunology now promises to transform the field.

Public squeamishness and ethical objections to breeding animals for organ transplants had also diminished, said Curtis, who argued that the moral arguments against xenotransplants were “hard to sustain . . . when you look at the outcomes for our patients”.

For a long time, xeno research focused on heart transplants, but now kidneys are leading the way to clinical approval. “A big advantage of the kidney is that if the transplant fails we can safely return the patient to dialysis,” said Curtis. “If the transplanted heart fails, there’s not much you can do.”

However, eGenesis and another leading US xenotransplant company, United Therapeutics, are working with hearts as well as kidneys. The FDA has approved a small xenoheart trial led by United Therapeutics.