Pig-Heart Transplants in Two Brain-Dead People Offer Chance to Improve Tests for Pig Viruses

Mr. Kelly was driving alone in his car when he suffered a heart attack, according to his fiancée, Alice Michael. Ms. Capuano, who had been the recipient of a kidney transplant from her son many years ago, had a heart attack while at home, said her husband, Richard Capuano.

Both individuals were later declared brain-dead and maintained on ventilators. Their families agreed to donate their bodies to science, to take part in the research studies. In the U.S., brain death is defined as the irreversible cessation of all brain function, even if heart and lung activity can be maintained with machines.

The studies focused on gathering data about how the pig hearts functioned as well as implementing a new set of strategies to test for and prevent the transmission of pig viruses—a longtime area of concern by the Food and Drug Administration that has intensified in the wake of the death of a Maryland man who in January was transplanted with a pig heart that was later discovered to have a pig virus in it.

In the NYU studies, researchers used a newly created infectious-disease protocol designed to help ensure that pig viruses weren’t transmitted to the research subjects who received the hearts or the team of health providers involved in the experiments.

The pig hearts weren’t immediately rejected by the recipients’ bodies and functioned for the duration of the three-day studies, according to Nader Moazami, surgical director of heart transplantation at NYU Langone Health, who led the pig-heart procedures. The data haven’t been published yet or peer-reviewed.

The possibility of pig viruses in organs causing serious or novel infections in human recipients and their family members, friends, medical caregivers, and the wider community, is considered one of the major risks in the field of xenotransplantation, or interspecies transplantation.

The issue was highlighted by the recent case of David Bennett, a 57-year-old handyman from Hagerstown, Md., whose pig-heart transplant was conducted at the University of Maryland Medical Center in Baltimore. The emergency procedure was aimed at extending the critically ill man’s life. Mr. Bennett died in March, 60 days after the transplant surgery.

The FDA, which regulates xenotransplantation, put the prevention of animal disease transmission to people at the top of the agenda during a two-day public advisory committee meeting about xenotransplantation convened last month. The FDA is devising plans to allow clinical trials testing the transplantation of pig organs into humans, a person familiar with the matter said.

The push for xenotransplantation is being driven by the continuing shortage of human organs. More than 100,000 people in the U.S. are on the national waiting list for organs, according to the United Network for Organ Sharing, a nonprofit that under contract with the federal government helps allocate organs, and more than 6,000 people die each year while waiting.

At the FDA advisory committee hearing, the scientists discussed which pig diseases should be tested before animal organs are transplanted into humans. In addition to pig CMV, the virus found in Mr. Bennett’s pig heart, scientists have suggested testing for several common pig viruses, such as porcine lymphotropic herpesviruses and porcine circoviruses, as well as porcine endogenous retroviruses, or PERVs, which are found in the genome of all pigs.

The genetically modified pigs used in the two NYU pig heart studies and in the Maryland emergency transplant procedure came from Revivicor Inc., a Blacksburg, Va., based company.

The NYU team has developed its own tests for porcine viruses in organ recipients, and is working to develop a test to determine whether a pig has been previously exposed to CMV even if there is no active infection, according to Dr. Sapna Mehta, director of the transplant infectious diseases program and clinical director of the NYU Langone Transplant Institute. In addition to concerns about well known pig viruses, scientists also worry about the potential risk of animal viruses that haven’t yet been identified, Dr. Mehta said.

Blood samples were taken from the two individuals who received the pig hearts and from members of the medical team involved in the studies, Dr. Mehta said. The samples are being stored so that if new pig viruses are identified years from now, researchers can test them and follow up with anyone who might have been exposed, she said.

Transplant infectious disease specialists are putting together a “white paper” suggesting ways to monitor for possible infections in the pigs and transplant recipients, according to Dr. Jay Fishman, director of the transplant infectious disease and compromised-host program at Massachusetts General Hospital, who is coleading the effort.

Muhammad M. Mohiuddin, a professor of surgery at the University of Maryland School of Medicine and one of the doctors involved in Mr. Bennett’s surgery, said that the scientists continue to study Mr. Bennett’s case to understand what role, if any, the pig virus in his heart may have played in his death.

Scientists went back to blood samples they stored and, using more sensitive tests, were able to detect the presence of the virus, Dr. Mohiuddin said. They also retested samples from baboons that received pig hearts and picked up several cases of the virus that had been previously missed in those experiments. The new data will be part of their discussions with the FDA later this summer seeking the agency’s guidance about what additional steps might be necessary to open human trials, Dr. Mohiuddin said.

In the NYU experiments, the surgeons made three modifications during the transplant surgery to enlarge the blood vessels from the pig heart because they were concerned the organ was too small to ensure normal blood flow in Mr. Kelly, Dr. Moazami said. Since Ms. Capuano was overall smaller physically, they only made one modification in the pig heart, the transplant surgeon said, adding that in the future, it might be possible to grow pigs to a range of sizes.

To address the ethical and safety issues involved with xenotransplantation, a special research oversight board at NYU reviewed and approved the studies, and the researchers also consulted with the New York State Department of Health, Dr. Moazami said.

As a further precaution against any possible infection transmission, the operating room, equipment, and instruments in the pig heart studies will only be used for future xenotransplantation research, Dr. Moazami said, adding that the extra steps they took are required because the potential transmission of a pig virus is also a public-health issue.

“If this is going to be applicable to a large patient population out in the world, that is the only way the public will trust this process,” he said.

Write to Amy Dockser Marcus at amy.marcus@wsj.com

Mr. Kelly was driving alone in his car when he suffered a heart attack, according to his fiancée, Alice Michael. Ms. Capuano, who had been the recipient of a kidney transplant from her son many years ago, had a heart attack while at home, said her husband, Richard Capuano.

Both individuals were later declared brain-dead and maintained on ventilators. Their families agreed to donate their bodies to science, to take part in the research studies. In the U.S., brain death is defined as the irreversible cessation of all brain function, even if heart and lung activity can be maintained with machines.

The studies focused on gathering data about how the pig hearts functioned as well as implementing a new set of strategies to test for and prevent the transmission of pig viruses—a longtime area of concern by the Food and Drug Administration that has intensified in the wake of the death of a Maryland man who in January was transplanted with a pig heart that was later discovered to have a pig virus in it.

In the NYU studies, researchers used a newly created infectious-disease protocol designed to help ensure that pig viruses weren’t transmitted to the research subjects who received the hearts or the team of health providers involved in the experiments.

The pig hearts weren’t immediately rejected by the recipients’ bodies and functioned for the duration of the three-day studies, according to Nader Moazami, surgical director of heart transplantation at NYU Langone Health, who led the pig-heart procedures. The data haven’t been published yet or peer-reviewed.

The possibility of pig viruses in organs causing serious or novel infections in human recipients and their family members, friends, medical caregivers, and the wider community, is considered one of the major risks in the field of xenotransplantation, or interspecies transplantation.

The issue was highlighted by the recent case of David Bennett, a 57-year-old handyman from Hagerstown, Md., whose pig-heart transplant was conducted at the University of Maryland Medical Center in Baltimore. The emergency procedure was aimed at extending the critically ill man’s life. Mr. Bennett died in March, 60 days after the transplant surgery.

The FDA, which regulates xenotransplantation, put the prevention of animal disease transmission to people at the top of the agenda during a two-day public advisory committee meeting about xenotransplantation convened last month. The FDA is devising plans to allow clinical trials testing the transplantation of pig organs into humans, a person familiar with the matter said.

The push for xenotransplantation is being driven by the continuing shortage of human organs. More than 100,000 people in the U.S. are on the national waiting list for organs, according to the United Network for Organ Sharing, a nonprofit that under contract with the federal government helps allocate organs, and more than 6,000 people die each year while waiting.

At the FDA advisory committee hearing, the scientists discussed which pig diseases should be tested before animal organs are transplanted into humans. In addition to pig CMV, the virus found in Mr. Bennett’s pig heart, scientists have suggested testing for several common pig viruses, such as porcine lymphotropic herpesviruses and porcine circoviruses, as well as porcine endogenous retroviruses, or PERVs, which are found in the genome of all pigs.

The genetically modified pigs used in the two NYU pig heart studies and in the Maryland emergency transplant procedure came from Revivicor Inc., a Blacksburg, Va., based company.

The NYU team has developed its own tests for porcine viruses in organ recipients, and is working to develop a test to determine whether a pig has been previously exposed to CMV even if there is no active infection, according to Dr. Sapna Mehta, director of the transplant infectious diseases program and clinical director of the NYU Langone Transplant Institute. In addition to concerns about well known pig viruses, scientists also worry about the potential risk of animal viruses that haven’t yet been identified, Dr. Mehta said.

Blood samples were taken from the two individuals who received the pig hearts and from members of the medical team involved in the studies, Dr. Mehta said. The samples are being stored so that if new pig viruses are identified years from now, researchers can test them and follow up with anyone who might have been exposed, she said.

Transplant infectious disease specialists are putting together a “white paper” suggesting ways to monitor for possible infections in the pigs and transplant recipients, according to Dr. Jay Fishman, director of the transplant infectious disease and compromised-host program at Massachusetts General Hospital, who is coleading the effort.

Muhammad M. Mohiuddin, a professor of surgery at the University of Maryland School of Medicine and one of the doctors involved in Mr. Bennett’s surgery, said that the scientists continue to study Mr. Bennett’s case to understand what role, if any, the pig virus in his heart may have played in his death.

Scientists went back to blood samples they stored and, using more sensitive tests, were able to detect the presence of the virus, Dr. Mohiuddin said. They also retested samples from baboons that received pig hearts and picked up several cases of the virus that had been previously missed in those experiments. The new data will be part of their discussions with the FDA later this summer seeking the agency’s guidance about what additional steps might be necessary to open human trials, Dr. Mohiuddin said.

In the NYU experiments, the surgeons made three modifications during the transplant surgery to enlarge the blood vessels from the pig heart because they were concerned the organ was too small to ensure normal blood flow in Mr. Kelly, Dr. Moazami said. Since Ms. Capuano was overall smaller physically, they only made one modification in the pig heart, the transplant surgeon said, adding that in the future, it might be possible to grow pigs to a range of sizes.

To address the ethical and safety issues involved with xenotransplantation, a special research oversight board at NYU reviewed and approved the studies, and the researchers also consulted with the New York State Department of Health, Dr. Moazami said.

As a further precaution against any possible infection transmission, the operating room, equipment, and instruments in the pig heart studies will only be used for future xenotransplantation research, Dr. Moazami said, adding that the extra steps they took are required because the potential transmission of a pig virus is also a public-health issue.

“If this is going to be applicable to a large patient population out in the world, that is the only way the public will trust this process,” he said.

Write to Amy Dockser Marcus at amy.marcus@wsj.com