The inaugural surgery to merge a mechanical cardiac assist device with a genetically modified pig kidney has been carried out at NYU Langone Health, the institution announced Wednesday.
The patient, Lisa Pisano, aged 54 from New Jersey, suffered from heart failure and end-stage renal disease necessitating regular dialysis, as detailed in a press release from NYU Langone. However, due to additional chronic ailments that "substantially diminished the prospects of a favorable outcome" and a severe shortage of donor organs in the United States, Pisano was ineligible for conventional heart or kidney transplants.
"When presented with this opportunity, I felt compelled to seize it," Pisano expressed during a press briefing from her intensive care unit bed.
"I've exhausted all other avenues. So, when this chance arose, I decided to embrace it," she remarked, aspiring to "cherish moments with my grandchildren and engage in playful activities with them."
The demand for organs far surpasses their availability. On a daily basis, 17 individuals in the United States perish while awaiting organ transplants, with kidneys being particularly scarce. According to data from the Organ Procurement and Transplantation Network, around 27,000 kidney transplants were conducted in 2023, yet nearly 89,000 individuals remained on the waiting list for these vital organs.
Experts assert that xenotransplants—implanting animal organs into humans—are indispensable in addressing the organ deficit. Genetic manipulation facilitates precise modifications to a pig's DNA to prevent the human body from identifying the animal's organs as foreign entities and rejecting them.
On April 4, Pisano received the cardiac assist device, followed by a genetically modified pig kidney, along with the pig's thymus gland, on April 12. Her case marks the first documented instance of an organ transplant in a recipient with a mechanical heart pump, as stated by NYU Langone. Moreover, it stands as the second recorded transplantation of a gene-edited pig kidney into a living individual and the inaugural instance of transplantation accompanied by the thymus gland.
The first recipient of a gene-edited pig kidney, 62-year-old Rick Slayman, received the organ at Massachusetts General Hospital in March and was discharged home this month. Additionally, pig hearts have been transplanted into two living individuals who succumbed within weeks of the procedure.
In addition to renal disease, Pisano suffers from congestive heart failure and has undergone heart stent placement and multiple catheterizations, as revealed in a video provided by NYU Langone. In 2020, she was diagnosed with colon cancer and underwent a significant portion of her colon's removal, according to her husband, Todd, in another video from NYU Langone.
"Pisano's condition was rapidly deteriorating, and realistically, her lifespan was limited to mere days or weeks," remarked Dr. Robert Montgomery, the head of the NYU Langone Transplant Institute who led the surgery, in a video from NYU Langone. During the press conference on Wednesday, he described her predicament as a "medical quandary."
"She was grappling with both heart and kidney failure but was unsuitable for a simultaneous heart and kidney transplant due to her other medical conditions," Montgomery elucidated.
Her medical team obtained approval from the US Food and Drug Administration to perform the novel procedures under its expanded-access or "compassionate use" policies, granting terminally ill patients lacking alternative options access to investigational medical treatments outside of clinical trials.
The kidney originated from a pig engineered to disrupt a gene responsible for producing a sugar present on the surface of animal cells known as alpha-gal, which can trigger human antibodies and prompt an immune response. The pig's thymus gland, involved in immune function, was positioned alongside the kidney in an effort to facilitate recognition of the organ by Pisano's immune system.
Montgomery highlighted that the gene modifications implemented in the pig in this case are significantly simpler than those employed in other xenotransplants in living humans. "We have a chance to truly tackle the organ shortage issue. The more intricate the gene alterations, the less feasible it becomes to propagate those edits within a population. Each pig would have to be cloned for each organ. This is not easily scalable. Hence, we believe simplicity is key in this scenario."
Although Pisano's journey ahead is lengthy, "her kidney is performing exceptionally well... Her heart function has significantly improved." Currently, medical professionals are vigilant for potential complications such as rejection and infections. They anticipate at least another month of rehabilitation before potential discharge.
Pisano recounted significant mobility issues prior to the procedures. "I struggled to even stand up and catch my breath. I was practically immobile," she recalled. Presently, she attests, "I feel the healthiest I've felt in a long while," expressing optimism regarding the outcome.
"In the worst-case scenario, if it doesn't succeed, it might benefit someone else," she reflected. "At least someone will derive benefit from it."
