Organ transplantation from animals to humans is a little closer. The North American company eGenesis has managed to keep a macaque alive for more than two years after removing both kidneys and transplanting a pig kidney, according to a study published this Wednesday in the journal Nature. Four other specimens survived more than a year after receiving the same intervention, for which the researchers genetically modified the donor pigs. The success opens the way to the first clinical trials in humans.
“These results are unprecedented, and represent a monumental step forward towards achieving human compatibility,” Mike Curtis, president and CEO of the entity that led the work, said at a press conference. “The data are crucial to advance our porcine liver donor candidate toward clinical trials” in humans, something the company will work toward “in the coming months” alongside the Food and Drug Administration (FDA). , the regulatory entity in the United States, has assured.
Transplants from animals to humans, called xenotransplants, are considered the great asset to end the global crisis of lack of organs, which kills about 19 people a day in Europe, but they have not yet been tested on people in protocolized studies. In Spain, a global benchmark when it comes to transplants, 2022 closed with almost 5,000 people waiting for a donor. Across the European continent as a whole, the waiting list rises to 60,000 people, and in the United States it shoots up 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 aimed at “humanizing” the organ, eliminating three problematic porcine genes and introducing 7 human ones. The objective of all these changes was that the macaques’ immune system did not identify the foreign organ as a foreign body and attack it.
The “humanization” of the kidneys, however, has not prevented the macaques from requiring immunosuppressive treatment to avoid rejection, something common and also essential in human-to-human transplants. The idea of ??these treatments is to soften the response of the immune system of the person receiving the kidney to, again, achieve the correct adaptation of the organ in the body of the transplant recipient. This regulation, therefore, cannot go beyond the limit, since if the patient’s defenses are weakened too much, opportunistic infections and other adverse effects could appear that would put her life at risk.
Until now, all xenotransplantation attempts that have achieved prolonged survival in primates have been accompanied by medication too intense to be applied in real life. The advance published this Wednesday has changed the paradigm, achieving for the first time that a macaque exceeded two years of post-transplant life with a suppression compatible with the standards required in humans.
The remaining 59 changes have served to eliminate any possibility of infection of the recipient with porcine viruses, inactivating the genetic sequences suspected of favoring it. “This is the only […] preclinical study in the field that has evaluated donors” who had so many modifications, explains Wenning Qin, supervisor of the study, in an email to La Vanguardia, who highlights that they have also achieved “the greatest documented survival with an immunosuppressive regimen that is translatable to the clinic.”
“We have done these studies to allow progress to the clinic,” that is, to studies in humans, the president of eGenesis explained at a press conference. The design of the work was carried out in accordance with what the North American FDA asked of them for this purpose: “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 which, in Curtis’ opinion, emerges from the results of this study.
In addition to the specimen that was over two years old, four other macaques (of the 15 operated on) survived a year or more. In all cases, a single transplanted kidney was able to compensate for the lack of the two natural organs, demonstrating that the procedure is effective.
Animal tests come with a series of difficulties that complicate a longer life for the recipients: the macaques cannot express how they are feeling, they are not able to have a post-surgery rest regime, and the operation is complicated because they are so many. smaller than humans. In fact, the main causes of death were opportunistic infections and injuries caused by surgery. “We barely saw any loss of kidney function due to rejection,” says the company’s CEO.
That is why the researchers consider that the preclinical work is done, and do not believe that “trying to continue extending the survival [of the animal receptors] is much more beneficial,” explains Curtis. The next step, he says, is “to achieve long-term survival when we jump to patients.”
