What is xenotransplantation, and how far away is it?

Researchers, doctors and scientists are one step closer to building a new way to treat people suffering from organ failure, thanks to a recent decision by the Food and Drug Administration (FDA).

The FDA has given approval to two companies to begin clinical trials for transplanting genetically modified animal organs into patients with kidney failure. It’s called xenotransplantation, and it could be a groundbreaking development for medical science. It is also a sign of hope for the more than 100,000 people currently waiting for a lifesaving transplant.

It’s a question that has interested experts across the healthcare industry. At UNOS, researchers have partnered with healthcare company Sanofi, as well as United Therapeutics Corporation, one of the companies given FDA approval to supply modified pig kidneys for clinical trials, to conduct research into the impact xenotransplant therapy could have on patients, doctors and the public.

Jennifer Wainright, UNOS senior research scientist, said now is the right time to explore public perception of xenotransplant, so any concerns can be addressed appropriately.

“We’re closer than we’ve ever been to this becoming a viable therapy, so it’s important to know if the idea of receiving a modified organ from a pig is something people are comfortable with,” Wainright said. “Is it something patients want? Do doctors have concerns about performing this type of transplant? That’s where our research is focusing.”

Within the past few years, several xenotransplants have occurred using genetically modified pig organs, but in all cases, the transplant has been performed under compassionate use rather than approved clinical therapy.

“Xenotransplantation is not an approved therapy,” Klein said. “The ones that have been performed (in a modern medical setting) have been a singular situation for someone who has no other option.” This means that so far, the only patients who have received an organ from an animal are patients who may have had difficulty finding a matching organ, who were running out of vascular access for dialysis, or who otherwise couldn’t receive an organ transplant from a human donor.

The first experiments with xenotransplantation took place more than 100 years ago, but more recently our growing knowledge of organs and immune systems has identified the obstacles in the way of making xenotransplantation a viable option for people in need of a transplant.

Klein says under our current understanding immunosuppression is half of the solution. This involves administering medications that reduce the strength of the patient’s immune system, so it is less likely to attack the donated organ. Currently all patients who receive a donated human organ must undergo some level of immunosuppression to prevent their body from rejecting the donation.

The second piece of the puzzle involves genetically modifying the animal organ. Genetic modification generally sets out to accomplish two things: preventing the donor organ from expressing molecules that would generate an immune response and incorporating human genes into the donor animal, so the donor organ is built of cells that are more representative of what human cells are like. Currently, researchers have focused on pig organs due to their size, the speed at which pigs grow and the similarities in how their organs function when compared to humans.

But even if the above techniques are perfected, more obstacles remain. Like any potential medical therapy, its efficacy will need to be proven in the upcoming clinical trials.

Doctors and researchers will need to demonstrate the durability of the animal organs in a human, and there will need to be more data indicating xenotransplants can be a successful therapy. Despite these challenges, doctors across the country feel a future where animal organs can dramatically reduce the transplant waiting list isn’t far off. Dr. Klein says the recent news is a welcome change from the forecasts he’s given when asked about xenotransplantation multiple times in his decades-long career.

“When I gave formal presentations at Johns Hopkins in the late 1980s, the question was posed to me, how soon until xenotransplantation is a viable option? At the time, there was encouraging scientific progress in the field, and I said, ‘It’ll be about five years.’ When I was a professor 30 years later, I was asked the same question and gave the same answer. If you asked me today, I’d say probably five years. The old saying is ‘the future of transplantation is xenotransplantation, and it always will be,’ but now we are much more confident that it might be here in the very near future.”

The first clinical studies will begin with just a handful of patients, but positive results could pave the way towards FDA approval. This next step is being seen as practical progress the entire medical community will be following in the years to come.