The University of Alabama at Birmingham Comprehensive Transplant Institute has been awarded a five-year, $19.5 million grant from biotechnology magnate United Therapeutics Corporation to launch a pioneering UAB Xenotransplantation Program that both groups hope will lead to genetically modified kidney transplants from pig models to humans by 2021.

Image/ UAB
Image/ UAB

“More than 8,000 people either died waiting for a kidney transplant or became too sick to receive a kidney transplant in 2014,” said Selwyn Vickers, M.D., senior vice president and dean of UAB’s School of Medicine. “As a research and medical community, we have to do more to try and help those suffering. This very generous gift from United Therapeutics will enable us to establish a unique research arm for the School of Medicine that gives us the chance to be the first in the world to transplant genetically engineered kidneys from nonhuman organs into human recipients within the next five years. This opportunity further defines our school and UAB Medicine as an outstanding destination for education, clinical care and research — all with the ultimate goal of securing the top medical and scientific talent in the country and becoming the preferred destination for patients in Alabama and across the country who need care.”

Xenotransplantation is any procedure that involves the transplantation, implantation or infusion into a human recipient of either live cells, tissues or organs from a nonhuman animal source or human body fluids, cells, tissues or organs that have had ex vivocontact with live nonhuman animal cells, tissues or organs, according to the U.S. Food and Drug Administration.

Joseph Tector, M.D., Ph.D., one of the leading xenotransplant researchers in the United States, has been recruited from Indiana University to run UAB’s xenotransplantation program. His first day at UAB was April 1. Tector was a professor of surgery in the IU School of Medicine and director of its transplant institute.

“Transplantation is one of medicine’s greatest triumphs, saving thousands of lives each year, and improving the quality of life for many of those fortunate enough to obtain a scarce graft from another person,” said Tector. “Unfortunately, the supply of human organs is insufficient to treat all the patients who present each year with organ failure, and who could benefit if a compatible graft were available. While substantial progress has been made toward harnessing the tremendous potential of stem cell biology and tissue engineering, most approaches based on these young technologies are at a proof-of-concept stage, and far from clinical application. These considerations provide a powerful impetus for preclinical translational research to develop clinical therapies using organ and islet xenografts, which I believe are close to making clinical impact.”

Xenotransplantation is not entirely novel. Pig heart valves have been used for many years without ill effect and seldom elicit rejection. UAB scientists believe whole organ transplants from genetically modified pigs are possible in the near future if immunological and physiological barriers can be overcome. Creating a xenotransplant program is another step in UAB’s commitment to academic and research excellence and clinical innovation for lifesaving treatments that reach beyond standard clinical techniques, said Herbert Chen, M.D., chair of the Department of Surgery and surgeon-in-chief of UAB Hospital.

“One of the things that makes UAB the best place in America to be a student, resident, faculty member and leader is that its people are fearless when it comes to trying to find solutions to complex problems facing our world today,” Chen said. “This will be daring work, and we are focused on bringing in the research and clinical talent necessary to discover if xenotransplantation will be a viable option for humans in the very near future. We believe it will be.”

Devin Eckhoff, M.D., director of UAB’s Division of Transplantation said the primary motivation for using genetically engineered kidneys from nonhuman resources is driven by supply, demand and cost.

In terms of supply and demand, Alabama has more than 3,400 residents in need of a kidney transplant, and more than 100,000 U.S. citizens total are waiting kidney transplants as of January 2016. All told, more than 121,000 people in the United States are waiting for lifesaving organ transplants of some type.

From a cost perspective, a recent article in the American Journal of Transplantation showed that the cost of dialysis treatments averages $1.45 million per patient over the course of a lifetime. According to the article, the net benefit for society from saving thousands of lives each year and reducing the suffering of 100,000 more who are receiving dialysis would be about $46 billion per year. In addition, it would save taxpayers approximately $12 billion each year.

Eckhoff said UAB’s current infrastructure, forthcoming infrastructure improvements and faculty and staff recruitment efforts will continue the Division of Transplantation’s growth efforts and stimulate more innovation zones in Birmingham and across Alabama.

“We want UAB to be the premier center for in-stage organ disease, whether it’s liver, heart or kidney, and there is no doubt that our list of those awaiting transplants — especially kidney transplants — is steep, and the cost of ongoing dialysis care is prohibitive,” Eckhoff said. “The average wait for someone with blood type O, the most common blood type, is six to eight years, so there is a real need. Even if you were to get 100 percent consent from every brain dead donor in America, you still wouldn’t have enough organs to fill the need. And here in the south, we’re in the hotbed of organ failure — kidney failure, liver failure. People are dying waiting on organs. Xenotransplantation is a natural fit for us as a university and could potentially spur more biomedical opportunities in our region.”

Advances in molecular biology and immunology have made the possibility of xenotransplantation appear more feasible in recent years. The goal for xenotransplantation is that it will be a long-term solution for patients, much like living- and deceased-donor donations, which Eckhoff emphasizes will remain as important as they are today, even if xenotransplantation efforts are successful; xenotransplantation is viewed as a supplement to living- and deceased-donor transplants.

“Organ donation is irreplaceable, but finding other avenues to increase options for those suffering from kidney disease and kidney failure is a must,” Eckhoff said.

UAB leads the nation in living donor transplantation and is a leading research center in providing novel therapies for long-term survivors. Its goal of providing innovative access to transplant has enabled UAB physicians to provide 12,000-plus transplants over five decades.