Surgeons perform the world’s first genetically modified pig kidney transplant on a living human at Massachusetts General Hospital.
MASSACHUSETTS GENERAL HOSPITAL
Biotech startup eGenesis has developed a genetically modified kidney that was successfully transplanted right into a living patient last week. The CEO says the corporate is just getting began.
From Alex KnappForbes contributor
LOn Thursday, surgeons at Massachusetts General Hospital announced that for the primary time a living human patient had received a kidney transplant from a pig. This scientific breakthrough represents hope for the handfuls of people that die on daily basis while waiting for an organ transplant, the hospital’s transplant director, Joren Madsen, said at a news conference following the announcement. “The dream of transplant researchers – the Holy Grail – was to use pig organs to complement human organs to solve the problem of organ shortage,” he said.
Of course, it wasn’t as easy as just going right down to the farm. The kidney was developed by Massachusetts-based startup eGenesis, which has been working for nearly a decade on gene editing pig organs so that they could be safely transplanted into humans. But CEO Mike Curtis told Forbes that this week’s milestone is just the start. His company, which has raised $291 million in enterprise capital thus far, goals to advance its gene-editing technology for kidney, liver and heart transplants into clinical trials in the following two years, making it a disruptive player in a market which is dominated by Grand View Research Estimates around 15 billion US dollars
“We showed that we actually have something that can help patients,” he said. “For me, it’s all about moving into this new age of science and helping people who have very few treatment options.”
There are currently over 100,000 people on the transplant waiting list within the United States, but resulting from the limited availability of donor organs, fewer than half of those will receive a transplant in a given yr. For many years, scientists have believed that animal organs could help some patients, even when only to maintain people alive long enough to receive a human organ. Pigs are a really perfect candidate for providing donor organs because they grow up quickly and their organs are similar in size and functionality to humans.
As scientists learn more about how pig organs work in humans, it could be possible to genetically engineer them to require fewer or no immunosuppressive drugs in comparison with a human organ.
MASSACHUSETTS GENERAL HOSPITAL
In this case, the patient was a 62-year-old man whose previously transplanted kidneys had failed, and the procedure was in a position to proceed under the Food and Drug Administration’s Expanded Access program, which allows patients with life-threatening diseases allows to profit from experimental drugs or procedures. This operation was followed by several different experiments using pig kidneys from brain-dead donors, in addition to two operations during which living patients received transplanted, genetically modified pig hearts.
Jamil Azzi, a transplant surgeon at Brigham and Women’s Hospital who was not involved in Thursday’s operation, praised the operation. “It’s a major breakthrough that’s been decades in the making,” he said Forbes. However, he cautioned that way more data is required before any such surgery becomes routine for human patients. A vital query is how long a donated pig kidney can last in a human patient. “If it fails in two to three months, we will be way behind,” he said. In 2023, two patients who received pig heart transplants developed by United Therapeutics subsidiary Revivicor died a couple of weeks after their surgeries, even though it shouldn’t be yet entirely clear why.
One of the largest challenges in an animal-to-human transplant is ensuring that the body of the person receiving the transplant doesn’t completely reject the animal organ. This is already an issue with kidneys donated by humans, and skeptics say the multitude of differences between pigs and humans would make such a transplant unimaginable. This is where gene editing comes into play. For last week’s surgery, Curtis explained, it was needed to genetically modify the donor pig’s kidney with seven different human genes, removing three pig genes and 59 additional pieces of DNA. These changes be certain that the kidney shouldn’t be attacked by the patient’s own immune system and rejection occurs, although as with human organs, immunosuppressive drugs are required.
These changes were made to a single pig cell, which was then incorporated into an embryo and cloned. The cloned embryos were then implanted right into a sow, which gave birth to piglets with the genetic changes.
Curtis explains that so many changes increase the chance that other parts of the animal’s genome might be unintentionally modified – so-called “off-target” changes. But lately, advances in genome sequencing have made it possible to detect whether off-target changes have occurred. In the case of this particular pig, the corporate was in a position to determine that such changes were minimal and had no impact on the end result.
In one Paper published In Nature Last fall, the corporate highlighted cases during which monkeys that received pig kidney transplants survived for over a yr – in a single case, even over two years. Between these data and the successful kidney transplant this yr, Curtis said eGenesis is making progress toward formally submitting an application to the FDA to start a full-scale clinical trial to implant additional porcine kidneys into humans as early as 2025. That’s not quite the case. But there’s nothing yet: Curtis said the agency desires to see much more primate data before giving the corporate the green light. Although more data is required, Azzi added that what has been learned thus far is a “good indicator” that the corporate is on the appropriate track.
One thing the corporate must do to scale, Curtis says, is get to the purpose where the pigs could be bred with donated organs as a substitute of getting to be cloned and implanted. George Church, co-founder of eGenesis and a genetics researcher at Harvard Medical School, told Forbes that this might also provide opportunities for a single pig donor to supply multiple organs to patients.
“Ultimately, the vision is to produce organs in pigs that do not require immunosuppression.”
Curtis said the corporate’s programs to organize pig livers and hearts for transplant into humans are closer to fruition, using the same process to kidneys. In January the corporate announced a successful operation Use of a genetically modified pig liver in a brain-dead patient, with the organ attached externally to the body. This procedure could help patients with liver failure survive for a couple of crucial days – long enough to receive a full transplant from a human donor.
Thanks to this success, Curtis said his company plans to submit an application to the FDA for its genetically modified livers and start clinical trials by the top of this yr. Eventually, the corporate goals to completely transplant its livers into living patients.
The goal of eGenesis is a everlasting kidney and liver transplant. But in relation to his heart program, he says eGenesis primarily targets pediatric patients for whom a pig heart could function a viable bridge until they’ll receive a human organ. Currently, he said, greater than 50% of kids who need a brand new heart die while waiting for a transplant. The company has currently observed baboons with genetically modified hearts surviving over 200 days thus far, and Curtis said he hopes this “could lead to progress toward pediatric heart transplantation either later this year or early next year.”
The company has even greater ambitions in the long run. “Ultimately, the vision is to produce organs in pigs that do not require immunosuppression,” Curtis said. That could mean transplant patients would not must take drugs that decelerate the immune system to stop rejection. While this keeps them alive, it also increases the chance of infections and cancer. “We know this requires additional technical effort, but we need the human data to determine what the technical implementation looks like.”
Genetics researcher George Church, a co-founder of eGenesis, added that the ability of genetic engineering would allow the corporate to develop “enhanced organs” along with organs that do not require drugs. For example, he said it is feasible to edit the genomes of pigs to “create organs that are resistant to multiple pathogens” and even organs that age more slowly. As proof of concept, he pointed to research in his laboratory at Harvard Medical School, the outcomes of which were peer-reviewed Published in Nature, where a straightforward genetic change made a species of bacteria proof against all known viruses. “Now we want to do it with pigs,” he said.
For the immediate future, the corporate might want to expand, which may also require more capital, Curtis said. The company has enough headroom until the top of 2026 and is already within the means of raising further funds, he said. Curtis hopes the successful operation shows potential investors that the corporate is on the appropriate track.
“This first living human kidney transplant validates our entire approach,” he said. “And it will allow us to not only bring the kidney forward, but also bring the liver and heart forward in parallel.”
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