Autopsy of the first xenograft of a genetically modified pig heart

Autopsy of the first xenograft of a genetically modified pig heart

In December 2021, the United States Medicines Agency (FDA) urgently authorized a group of Baltimore scientists to embark on a risky and unprecedented undertaking: to transplant a genetically modified pig’s heart into a seriously ill 57-year-old patient, ineligible for a human gift, and doomed. died two months after the transplant performed on January 7; his surgeons have since worked to understand the causes of his death. The answer is complex, according to the first results of this investigation still in progress, published on Wednesday June 22 in the journal New England Journal of Medicine.

The organ implanted in David Bennett came from an animal “manufactured” by the American company Revivicor, carrying ten genetic manipulations. Cloned, selected, separated from its mother and its congeners over two generations, this animal was supposed to be “clean”, that is to say without virus, nasal PCR test in support. But the precautions were insufficient. At 20e day after the transplant, analyzes revealed the presence of DNA from a porcine cytomegalovirus (CMV) in blood samples taken from David Bennett, who was doing quite well. At 50e day after the transplant, his condition is deteriorating rapidly despite the battery of treatments he is receiving, including antivirals. His heart is failing, circulation and oxygenation of the blood must be supplemented by an extracorporeal machine. He died on March 8.

No signs of rejection

Cardiac ultrasound on days 19 and 49 revealed thickening of the lining of the ventricles of the heart, and analysis of cardiac tissue after biopsy showed deterioration after 50e day, with approximately 40% necrosis of cardiac muscle cells. When he died, his heart had doubled in size. But no typical signs of a rejection were observed, according to the American team. The presence of the porcine virus in the patient’s heart and blood may have played a role in the heart failure. Further testing is ongoing as human herpes virus 6 was found in David Bennett’s lungs and may have reacted with CMV.

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This virus problem should have been avoided. According to Nicolas Müller, specialist in immunology in human transplantation at the University of Zurich, the preventive tests carried out on the pig were not complete: “The search for viral DNA in a nasal sample by PCR in a healthy animal is not sufficient because it can be negative and still carry the virus. It would be necessary to do a serology for the search for antibodies against CMV in the blood, but these tests are not developed for the pig. »

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