All of the following collected information will be applied when ready for the next xenotransplantation patient. That includes clues about how to avoid problems that may have contributed to the heart failure, including a response to a drug aimed at preventing rejection.
“We are still figuring out what went wrong; we don’t have any answers,” said Muhammad M. Mohiuddin, co-leader of the pig heart study and professor of surgery and scientific/program director of the heart xenotransplantation program at the medical school.
“But we don’t consider this a setback,” he said. “We believe that he experienced the first victory through the surgery. When he seemed to recover for two months and to do well, we considered that a really great success. If we could have found out the reason why his heart suddenly gave out , he might have walked out of the hospital.”
An autopsy found that Bennett’s body showed no traditional signs of heart rejection. Instead, doctors found a thickening and then stiffening of the heart muscle, perhaps a 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-bred pig that evaded precautions and screening. It’s still not clear whether that contributed to the heart failure.
Bennet, 57, was bedridden for eight weeks and connected to a life-saving heart-lung bypass machine with end-stage heart failure before the genetically modified pig heart transplant. He was not eligible for a traditional heart transplant, and federal regulators granted him a “compassionate use” exemption to undergo the experimental pig heart transplant. Such organ transplants in animals are not approved by the Food and Drug Administration.
For now, more such transplants will be considered “on a case-by-case basis,” according to a statement from an FDA spokesperson to the Baltimore Sun.
The agency would not comment on if and when regulators would allow human trials, which typically involve larger numbers of transplant patients, multiple hospital locations, and data collection for the purpose of approval for the procedure. The Wall Street Journal, citing “sources familiar with the matter,” reported last week that the FDA was coming up with such plans.
FDA officials admitted to the sun that it is necessary to address the shortage of organs for transplantation.
“Xenotransplantation is an option to address the shortage of human allografts and organs for transplantation,” said an FDA spokesperson.
But the FDA also cited the complexity and risk of animal transplants, including transmission of infections, and the need to “carefully assess” those risks compared to the potential benefits in a trial.
“In general, the FDA will not allow an investigational product to be used unless it believes such risks are appropriately minimized and acceptable for the clinical situation,” the spokesperson said. “Due to the potentially serious public health risks of potential zoonotic infections, the FDA has instituted policies such as long-term patient monitoring and bans on blood donation to reduce the risk of infectious disease transmission.”
Mohiuddin said doctors have been in touch with the FDA about human trials, but said there would be more animal studies in the meantime.
“I think the presentations that have been made to the FDA by those in the field indicate that the best way forward is through a human clinical trial,” he said. “We are curious to see how the FDA will respond to this input and whether they will issue new guidance on this. From now on, we will continue with additional primate studies to see what else we can learn.”
But Mohiuddin said doctors already know the findings from Bennett’s transplant will lead to changes in practices and techniques in future human transplants.
Patients and their families have been in touch with him and other doctors since the transplant was announced, but there is no timeline to apply for approval for another transplant.
“There is a patient population that could benefit from this, and many have volunteered for the procedure,” he said. “Before we please someone else, we must be happy 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 Revvivicor to study its genetically modified pig UHearts in baboons.
About 110,000 Americans are waiting for an organ transplant, and more than 6,000 die each year while on the list, according to federal figures.