On January 10, the University of Maryland School of Medicine announced that it had successfully transplanted a genetically-modified pig heart into a patient with life-threatening arrhythmia, a disorder that affects the rate or rhythm of heartbeats.
The patient, David Bennett (57), was deemed ineligible for a conventional heart transplant or an artificial heart by leading transplant centres after a review of his medical records.
“It was either die or do, this transplant. I want to live. I know it’s a shot in the dark, but it’s my last choice…I look forward to getting out of bed after I recover,” he said a day before the surgery, according to a release from the University of Maryland School of Medicine.
The release added that he was doing well three days after the transplant.
Cross-species transplant
Xenotransplantation, or transplanting organs across different species, was first tried in humans in the 1980s. The experiment was abandoned after the famous case of the American Baby Fae who was born with a congenital heart defect and received a baboon heart in 1984.
The surgery was successful, but the baby died within a month of the transplant after it was rejected by her body’s immune system.
However, pig heart valves have been used for replacing damaged valves in humans for over 50 years now.
Xenotransplantation, if found compatible in the long run, could help provide an alternative supply of organs to those with life-threatening diseases. According to the US Department of Health and Human Services, 17 Americans die each day waiting for an organ transplant.
Genetically engineered pig
The donor pig underwent 10 genetic modifications, by which the genes responsible for the rapid rejection of foreign organs by the human body were inactivated or knocked out.
Four pig genes were removed, and six human genes were added.
“GalSafe” pigs, or pigs that had undergone editing to knock out a gene that codes for Alpha-gal (a sugar molecule) were used. Alpha-gal can elicit a devastating immune response in humans.
GalSafe pigs have been well studied, and are approved by the US Food and Drug Administration (FDA) for use in pharmacology.
“Building on the GalSafe platform, two other carbohydrate antigens were eliminated by knockout of the CMAH and Beta-4-Gal genes of the pig. To maintain a human-sized organ, the growth hormone receptor gene was also knocked out,” a spokesperson for the University of Maryland School of Medicine told The Indian Express in an email.
“Two human complement inhibitor genes (CD46 and DAF), two human anti-coagulant genes (EPCR and Thrombomodulin), and two human immune-modulating genes (CD47 and HO1) were inserted in a targeted fashion into the genome of the donor pig,” the spokesperson said.
The pig was provided by Revivicor, a regenerative medicine company. On the morning of the surgery, the team removed the pig’s heart and placed it in a special machine to keep the heart preserved until surgery.
Immunosuppressants for patient
As rejection was the main concern, the patient was put on the maximum rate of suppression from conventional anti-rejection drugs.
He was also given a new experimental drug to prevent his body from rejecting the pig’s heart.
The US FDA had granted emergency authorisation for the surgery through its expanded access (compassionate use) provision. According to the FDA, the compassionate use provision is applicable when an investigational device is the only available option for a patient with a life-threatening disease or medical condition.
Need for future studies
The spokesperson said the medical team was looking at the patient’s blood pressure and pictures of the heart under echocardiogram, and would be taking biopsies. These are routine checks similar to other human transplant recipients.
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“There are no signs of rejection at this point. The patient will be monitored for weeks and likely months. They are monitoring him for antibodies in the first stage and everything is going well so far. They will soon start monitoring for cell-mediated rejection, which can occur several days or weeks after transplant,” the spokesperson said.
“This was a breakthrough surgery and brings us one step closer to solving the organ shortage crisis. There are simply not enough donor human hearts available to meet the long list of potential recipients,” Dr Bartley P Griffith, MD, who surgically transplanted the pig heart into the patient, was quoted as saying in the release.
In a statement, Dr Robert Montgomery, who led a team that transplanted a pig kidney into a brain-dead human last year, said: “This is a truly remarkable breakthrough and takes what we did in September of 2021 to the next level. As a heart transplant recipient myself with a genetic heart disorder, I am thrilled by this news and the hope it gives to my family and other patients who will eventually be saved by this breakthrough.”
Members of the surgical team at University of Maryland School of Medicine show the pig heart for transplant into patient David Bennett in Baltimore on Friday. (AP) 
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