Since Friday, January 7, a 57-year-old man has been living with a genetically modified pig heart. This world first in terms of xenografting – that is to say transplantation from another animal species – was announced Monday, January 10 by a team from the University of Maryland (United States).
David Bennett, who has end-stage heart failure and arrhythmia, was not eligible for a conventional heart transplant, or even an artificial heart pump system. The Food and Drug Administration (FDA) therefore authorized this experimental strategy on a compassionate basis, in this consenting patient and without any other therapeutic option.
While the still very limited decline in the intervention led by surgeons Bartley Griffith and Muhammad Mohiuddin calls for caution, this first pig heart transplant is already recognized as an important step on the long road to xenotransplantation. The patient’s survival beyond 72 hours with a functional heart means that there has been no hyperacute rejection of the organ, one of the main risks of transplants between species.
This success comes a few months after another first in this field, also in the United States. On September 25, 2021, a team from Langone University (New York) had transplanted a pig kidney into a human for three days without observing immune rejection. The setting, however, was quite different: it was a brain dead woman, and the foreign kidney was connected to her vessels without being re-implanted in her abdomen.
“A real feat”
The modifications of the porcine heart carried out by Revivicor (the American firm also at the origin of the genetically modified kidney) relate to a total of ten genes. If the press release from the American University of Maryland remains discreet on the technique used to make this heart called Uheart, it specifies that “Three genes responsible for the rapid rejection of pig organs by humans, via antibodies, have been “eliminated” in donor pigs’. Furthermore, “Six human genes responsible for immune acceptance of the pig heart have been inserted into the genome”. Finally, an additional gene has been eliminated in the animal, “In order to avoid excessive growth of heart tissue in pigs”. The patient is now receiving immunosuppressive treatment, also experimental.
“This is a real feat, obtained thanks to DNA scissors such as CRISPR-Cas9, which make it possible to “purifier” genetically from pigs with great precision, and thus cross the species barrier by providing organs that can be used in human transplantation ”, greets Doctor Benoit Averland, Deputy Director of the Biomedicine Agency. According to him, the American team succeeded by playing on two tables: preventing hyperacute rejection, which is one of the main challenges of xenografts, but also protecting the recipient from the risk of infections by porcine retroviruses, another pitfall of transplants. from pigs. “Of course, we must remain cautious because the hindsight is still modest, we will have to see what becomes of this patient in the weeks and months to come., tempers Doctor Averland. It is also possible that this xenograft is not final and allows it to pass a milestone, making possible a transplant of a human heart in a second step “.
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Transgenic pig heart transplanted into human