Organ transplantation from animals to humans is a little closer. The American company eGenesis has managed to keep alive for more than two years a macaque whose two kidneys were removed and a pig transplanted, according to a study published yesterday in the journal Nature. Four other specimens survived more than a year after receiving the same intervention, in which the researchers genetically modified the donor pigs. The success paves the way for the first clinical trials in humans.
"These results are unprecedented, and they mean a monumental step forward towards achieving human compatibility", says Mike Curtis, president and executive director of the organization that has led the work. "The data is crucial to advancing our porcine liver donor candidate toward clinical trials" in humans, a goal the company will work on "in the coming months" with the FDA, he says.
Animal-to-human transplants, called xenotransplants, are seen as the big bet to end the global organ shortage crisis, which kills around 19 people a day in Europe, but have yet to be tested on humans in protocolized studies . In Spain, the global leader in transplants, 2022 was closed with almost 5,000 people waiting for a donor. On the European continent as a whole, the waiting list rises to 60,000 people, and in the United States it soars to over 100,000.
The kidney presented in the journal Nature contains a total of 69 genetic edits made with the CRISPR-Cas 9 tool, an unprecedented milestone in the field. Ten of the modifications have been intended to "humanize" the organ, removing three problematic porcine genes and introducing seven human ones. The aim of all these changes was to prevent the macaques' immune system from identifying the foreign organ as a foreign body and attacking it.
This regulation, in any case, cannot be overstepped, since if the patient's defenses are weakened too much, opportunistic infections and other adverse effects could appear that would put his life at risk.
Until now, all attempts at xenotransplantation that had achieved long survival in primates had been accompanied by medication that was too intense to apply in real life. This new breakthrough changes the paradigm, and achieves for the first time that a macaque exceeds two years of life post-transplantation with a deletion compatible with the standards required in humans.
The remaining 59 changes have served to eliminate any possibility of an infection of the recipient with porcine viruses, thanks to the inactivation of the genetic sequences suspected of being able to favor it. "This is the only [...] preclinical study in the field that has evaluated donors" who carried so many modifications, Wenning Qin, supervisor of the study, explains in an email to La Vanguardia, who emphasizes that, in addition, have achieved “the highest survival ever documented with a clinically translatable immunosuppressive regimen”.
"We did these studies to allow progress in the clinic", that is to say, in human studies, explained the president of eGenesis in a press conference. The design of the work was carried out in accordance with the requirements of the FDA: "The general feeling is that they are looking for a survival of at least 12 months in non-human primates, which shows both safety and efficacy", something that , according to Curtis, is drawn from the results of this study. The researchers consider that the preclinical work is done, and they do not believe that "trying to continue prolonging the survival [of animal receptors] is much more beneficial", explains Curtis. The next step, he says, is to "achieve long-term survival when we jump to patients."
