Third Party Pig to Human Kidney Transplant

In another sign that xenotransplantation is becoming a reality, medical teams at NYU Langone Health announced Tuesday that they have transplanted a genetically engineered pig kidney into a living patient for the third time.

Surgeons performed the surgery on November 25th over a period of seven hours. The recipient of the organ, a 53-year-old woman named Twana Rooney, lives in Alabama and has been on the waiting list for kidney surgery since 2017. In the late 1990s, Rooney donated a kidney to her mother. Years later, her remaining kidneys began to function, damaged by high blood pressure caused by pregnancy complications. Because of the high levels of antibodies in her blood, the chances of finding a compatible organ donor were very low.

After the surgery, Rooney no longer needed dialysis for the first time in more than eight years. She was discharged from the hospital on Dec. 6 and was fitted with a wearable tracker that sends her heart rate, blood pressure and other health data to her medical team. She is returning to the hospital daily for in-person evaluations and is expected to go home within three months.

“I'm very happy. I'm happy to receive this gift, a second chance at life,” Rooney said at a news conference Tuesday morning at a New York City hospital. “I have so much energy and an appetite I haven't had in eight years. It's like I can feel the blood flowing through my veins. When I put my hand on this kidney, I feel it buzzing. You can. It's very strong.”

This is the third time doctors have performed a kidney transplant using organs from genetically modified pigs. In April, the same team at New York University Langone treated Lisa Pisano, a 54-year-old New Jersey woman with both kidney and heart failure, who was fitted with a pig kidney just days after implanting a mechanical heart pump. . However, insufficient blood flow soon damaged the kidney, forcing surgeons to remove it six weeks later. Pisano was then placed in hospice care and died in July.

For both NYU transplants, the kidneys were donated by Livivicore. Livivicol is a biotechnology company spun off from the British company that produced the first cloned animal, Dolly the sheep. The company was later acquired by United Therapeutics. In Pisano's case, the kidneys came from an animal engineered to disrupt just a single gene for a cell-surface sugar known as alpha-gal, which can cause organ rejection by the human immune system. Ta. The kidney Rooney received was from a pig that had 10 different modifications to its DNA, including the removal of two additional genes: a molecule that turns on the human immune system and a pig growth hormone receptor.

In March, medical teams at Massachusetts General Hospital performed the first-ever surgery using an artificial pig kidney manufactured by eGenesis. Cambridge, Mass.-based eGenesis used CRISPR technology spun out of George Church's Harvard lab to create a herd of Yucatan minipigs carrying 69 DNA edits. As with Revivicor's animals, these modifications include knocking out genes for molecules that trigger the immune system and adding genes to make the organs more compatible with the human circulatory system. Unique to eGenesis are dozens of examples of cutting out latent viral DNA woven into pig genomes, edits that eradicate the risk of pig viruses accidentally jumping into humans.

The recipient of the organ, a 62-year-old man named Richard Suleiman, recovered enough to be discharged home two weeks after surgery. But two months later, in May, he died of an “unexpected cardiac event” that doctors said was unrelated to the transplant.

Although research into xenotransplantation has experienced a resurgence in recent years, the technique is still experimental and available only to patients who are too sick to qualify for a human organ. Three kidney transplants from genetically modified pigs were approved under the Food and Drug Administration's Compassionate Use Program for patients at risk of death without treatment.

Rooney presents a somewhat unique case, and doctors hope hers will lead to better outcomes and more insight into the field of xenotransplantation. Her high antibody levels made the chance of finding a suitable human donor nearly impossible, but she did not face death.

“This will give us a better understanding of what to expect in clinical trials involving patients in better general health,” Robert Montgomery, director of New York University's Langone Transplant Institute, said in an interview with STAT. “It will be,” he said in an interview with STAT. Rooney's progress will hold many lessons about the risk of rejection, the longevity of organs, and what human kidneys can do that pig kidneys can't.

“We need to monitor events over a longer period of time to better understand how these organs function over time,” said Montgomery, who directed the surgery.

It will take years of clinical trials to prove whether xenotransplants really work for patients and are a viable solution to the nation's organ shortage. There are currently more than 100,000 people on the U.S. transplant waiting list, most of them in need of a kidney. Thousands of people die every year while waiting.

eGenesis raised funding in September $191 million new The goal is to advance CRISPR-engineered pig kidneys toward human testing. CEO Mike Curtis told STAT that the company expects to ask the FDA for permission to begin formal clinical trials in the second half of 2025.

A spokesperson for United Therapeutics told STAT that the company plans to file its own IND application to begin clinical trials of the 10-gene-edited kidney “soon.”

The next few weeks will be crucial for Rooney. Pre-procedure tests showed she had moderate levels of so-called “xenoantibodies” (immune molecules primed to recognize and react to pig organs), but after she died last week, Autopsy showed activation of the complement system. This is a network of proteins that enhances (or complements) the action of antibodies, but in the case of xenografts, can cause harmful inflammation and clotting. “This may be an early sign that some antibodies may be being released against the kidneys,” Montgomery says.

Mr. Rooney is currently receiving additional complement inhibitors to alleviate this symptom and prevent the development of a potential rejection reaction. Her medical team said there are a number of additional medications available to reverse rejection if signs of rejection begin to be observed. The long-term goal is for Rooney to eventually be weaned off the most powerful immunosuppressants as she adapts to her new organ, but she will always be on some type of immunosuppressant.

Rooney said she is looking forward to being able to travel again and spend more time with her family and grandchildren. She has another goal after the transplant. “I want to go to Disney World,” she said with a laugh.