GlycoNet Investigator develops first-of-its-kind heart transplant procedure that can open the door for hundreds more

From ASTech.ca

In 1996, a baby was diagnosed in utero with a lethal heart condition. There was a possible pathway forward, but the procedure had never been performed. The potentially life-saving procedure would be a blood type mismatch heart transplant, the first of its kind and one that went against all accepted clinical practice at the time.

A blood type mismatch transplant would result in a lethal rejection of the donor heart in an adult, but the science suggested this would not be the case for the infant because of the baby’s immature immune system. The science was sound and the medical team believed the procedure offered the best path forward. On Valentine’s Day 1996, the team performed the first intentional blood type mismatch heart transplant in the world. That child is now healthy and the success of that first procedure opened the door for hundreds more infant transplant procedures globally.

Dr. Lori West led the team that made this fundamental discovery to transplant immunology.

“Someone has to be the first,” says West. “It can be very scary but if you are certain of the science then you do everything you can to move it forward and that’s what we did.”

West is a professor of paediatric surgery and immunology at the University of Alberta, Director of the Alberta Transplant Institute and Director of the Canadian National Transplant Research Program.

All her clinical care and scientific pursuits are fuelled by a passion for the patients. West says, “Watching that boy grow up into now a fine young man with a very bright future ahead of him, a healthy individual who is now a contributing member of society, has really been a rewarding experience for me personally, as a clinician, as a scientist and a parent myself.”

Complementary approach

As a both a clinician and a scientist, West’s work focuses on organ donation and transplantation clinical care and the scientific research behind it with both sides being completely complementary. She works clinically in pediatric heart transplantation, caring for children who range in age from a few hours old to early adolescence, with patients awaiting transplants and post-transplant. In her research, West expands on the care currently available into research that offers new hope by making the lives better of transplant patients.

West’s work extends beyond the children she treats. She explains, “There are four major pillars, as we call them, of health-related research. Those range from very basic science, to clinical work, to health systems and policy research and to population-based research. The work that I direct in my own laboratory, my research group as well in the Alberta Transplant Institute and in the National Transplant Research Program cover very broadly the entire breadth of research in donation and transplantation—well beyond children, well beyond heart and into a broader aspect that will really position us well to have a major impact on health care for some of our most vulnerable patients in Canada.”

The field of organ donation and transplantation is especially critical for West’s youngest patients. With available organs so rare for such young patients and the diagnoses often dire, the percentage of infants waiting for life-saving transplants is very high.

Prior to the discovery made by West and her colleagues, the mortality rate of infants on the transplant waiting list was over 50 per cent. Thanks to the new procedure, West says the rate has dropped to less than 10 per cent.

Improving patient outcomes

The work of a scientist is never over; progress gives rise to new questions. West is currently researching ways to improve the long-term care of transplant patients by finding ways to limit the need for immunosuppressant medicines.

All transplant patients take immunosuppressant drugs for the rest of their lives. Although they are very helpful in many ways, they also produce very difficult side-effects, especially when the transplant occurs very early in life.

“If we could somehow find a way to use fewer of these medicines or use them in a more refined way then we could avoid some of these difficult side-effects,” West says.

For more than 30 years, researchers have been trying to find ways to modify the immune system of transplant recipients to either use fewer of these drugs or none at all. This area is called immune tolerance.

In recent years, regulatory T-cells have been a topic of interest toward the goal of immune tolerance. These are specialized cells we all have that prevent autoimmune diseases. Now, they are being explored as a natural immunosuppressant by taking these cells from the body into the lab to grow into sufficient quantities. The cells are then put back into a transplant patient to theoretically suppress the immune response to an organ transplant.

While this work is being conducted around the world, West made a breakthrough in 2016 addressing the primary challenge about the sparseness of these cells in the body. West discovered that the answer might be found in an organ in the chest called the thymus that is removed and discarded during any heart surgery (including heart transplants), to allow the surgeon to reach the heart..

“The discovery that we’ve made is that these discarded thymuses are an incredibly rich source of abundant and potent regulatory T-cells,” explains Dr. West. “We’ve been studying the thymuses that are regularly thrown away; we take them into the lab and isolate these regulatory T-cells right from the source.”

This discovery is also very exciting because of its potential to treat not only transplant rejection but also many more patients who suffer from autoimmune diseases.

“Since these cells can suppress immunity to transplants the theory is that they can also suppress autoimmune diseases like diabetes, rheumatoid arthritis and many other autoimmune diseases that plague our patients around the world.”

Working together

Much of the success of recent transplant and immunology research has come from a team-based approach to science, which West encourages through all her pursuits.

“What’s really exciting is to bring scientists from disparate fields together. Although they may not speak the same language initially, if you give them the potential to develop synergies between what they do—with what they know really well—and with what they may not understand in another area of science, innovative ideas can blossom. You bring them together and say, ‘Is there a commonality that could be worked on together?’”

Based on the success of the collaboration between West and her colleagues with chemists at the University of Alberta, West began developing a framework for a national research program in transplantation in Canada.

“This network of several hundred individuals working at more than 30 sites around the country is built around a structure that breaks down silos and facilitates interactions, resulting in amazing synergies,” West says. ““Canada has wonderful scientists doing highly impactful science and we seem to embrace collaboration in a remarkable way and with enthusiasm for working in a collaborative environment. This can be incredibly productive.”

The national program, housed at the Alberta Transplant Institute, is becoming internationally recognized for the way the teams collaborate to increase the overall impact, speed and effectiveness of the science.

West is looking toward the future to combine gene therapy, artificial intelligence, engineering, health economics and many other collaborative applications to ensure transplant research continues to grow, generating new knowledge to benefit patients worldwide.

This article is republished from ASTech Foundation.

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