News that surgeons at the University of Maryland Medical Center had implanted a genetically modified pig’s heart into a human rocked the medical world earlier this year. But it didn’t surprise Children’s of Alabama cardiothoracic surgeon David Cleveland, MD, MBA, who is leading a similar xenotransplantation program at Children’s and the University of Alabama at Birmingham (UAB).
The program focuses on developing genetically modified solid organs from pig models for transplantation. To date, Cleveland’s team has successfully transplanted a genetically modified pig kidney into a brain-dead patient. The kidney produced urine.
Three years ago, Cleveland presented preliminary results from a study showing little reactivity in an infant’s blood to cells from a triple-knockout (TKO) pig. The pig had been genetically modified to delete the three major antigens that react with natural human anti-pig antibodies. Even those human cells that did react demonstrated a very mild reaction.
Back then, Cleveland said the next step was a transplant in a non-human primate, something required before the FDA would approve human trials.
Now he’s done it. So far, Cleveland and his team have implanted four infant baboons with the genetically modified pig hearts, with one of the animals living as long as eight months. In humans, the goal isn’t to have the heart last a lifetime but, rather, just long enough for a human heart to become available for transplant.
“I think we have to consistently demonstrate a four-to-six-month survival in non-human primates before the FDA approves a clinical trial,” Cleveland said. The team plans to implant more animals with the hearts this fall and is working on several grants to continue funding the study. Cleveland hopes to be able to submit the design for a clinical trial to the FDA sometime in 2024. In the meantime, he and his team published the results of the first baboon study in The Annals of Thoracic Surgery.
It’s quite possible, however, that the first transplant might occur outside a clinical trial with a humanitarian device exemption from the FDA. The authorization allows a device—in this case, the pig heart—to be used without showing effectiveness in formal clinical trials. That’s how the patient at the University of Maryland Medical Center was able to receive his heart.
“But our goal, ultimately, is to participate in an NIH-funded clinical trial,” Cleveland said, adding that those trials are conducted in more patients with strict safety monitoring and comprehensive data collection.