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Any information subsequently gathered is applied when ready for the next xenograft patient. These include clues about how to prevent problems that may have contributed to the heart failure, including a reaction to a drug aimed at preventing rejection.
“We’re still trying to figure out what went wrong; we don’t have a single answer,” said Muhammad M. Mohiuddin, co-leader of the pig heart study and professor of surgery and scientific/program director of the cardiac xenotransplantation program at the School of Medicine.
“But we don’t see it as a setback,” he said. “We think he survived the surgery as the first win. When he seemed to be recovering and doing well for two months, we really thought it was a huge success. If we could have identified the reason for his sudden cardiac arrest, he might have walked out of the hospital.”
An autopsy revealed Bennett’s body showed no traditional signs of cardiac rejection. Rather, doctors noted a thickening and then stiffening of the heart muscle, possibly in response to a drug used to prevent rejection and infection. As a result, it could not relax and fill with blood as it should.
According to the doctors’ study, published in June in the New England Journal of Medicine, they also found DNA from a latent infection in the specially reared pig that eluded precautions and screening. It is still unclear whether this contributed to the heart failure.
Bennet, 57, had been bedridden for eight weeks with end-stage heart failure and on a life-saving cardiopulmonary bypass machine prior to his genetically modified pig heart transplant. He was not eligible for a traditional heart transplant and federal authorities granted him a compassionate use exemption for experimental pig heart transplantation. Such animal organ transplants are not approved by the Food and Drug Administration.
An FDA spokesman told the Baltimore Sun that other such transplants will be reviewed “on a case-by-case basis” for the time being.
The agency declined to comment on whether and when regulators would allow human trials, which usually means larger numbers of transplant patients, multiple hospital sites, and data collection with the aim of approving the procedure. The Wall Street Journal reported last week that the FDA is preparing such plans, citing “sources familiar with the matter.”
FDA officials conceded to the Sun that the shortage of organs for transplantation needs to be addressed.
“Xenotransplantation represents an option to address the shortage of human allografts and transplant organs,” said an FDA spokesman.
However, the FDA also noted the complexity and risk of animal transplants, including the transmission of infections, and the need to “carefully evaluate” those risks versus the potential benefits in each study.
“Overall, the FDA will not allow use of an investigational drug unless it believes such risks are appropriately minimized and acceptable for the clinical setting,” the spokesman said. “Because of the potentially serious public health risks posed by possible zoonotic infections, the FDA has implemented guidelines such as long-term patient surveillance and a ban on blood donation to reduce the risk of infectious disease transmission.”
Mohiuddin said doctors have been in touch with the FDA regarding human studies, but said there would be more animal studies in the meantime.
“I think the presentations from experts at the FDA indicate that the best way forward is through a human clinical trial,” he said. “We are curious to see how the FDA will react to this input and whether they will issue new guidelines on this. From now on we are conducting additional primate studies to see what else we can learn.”
But Mohiuddin said doctors already know the results of Bennett’s transplant will lead to changes in practices and techniques in future human transplants.
Patients and their families have contacted him and other doctors since the transplant was announced, but there is no timeline to seek approval for another transplant.
“There is a patient population that could benefit, and many have volunteered for the procedure,” he said. “Before we can satisfy others, we must be satisfied that what we have learned can be applied to the next.”
The transplant was the result of a $15.7 million research grant from Virginia-based biotech company Revovicor to study its genetically engineered porcine UHeart in baboons.
About 110,000 Americans are waiting for an organ transplant, with more than 6,000 dying annually while on the list, according to federal figures.
