“It’s going to become a big, big deal,” said Dr. Marcelo Cypel, surgical director of the Ajmera Transplant Centre at Toronto’s University Health Network, and senior author of the study. “We’ll create a much more equal and fair distribution of donor organs to patients on the waitlist.”
The proof-of-concept study, conducted in Toronto and published on Wednesday, has demonstrated the possibility of safely converting blood type in donor organs for transplantation, which would not only make the wait shorter for patients, but also decrease mortality.
Here’s how it currently works
Currently, among other factors, patients are matched with a donor based on blood type, which in many cases can make waiting a whole lot longer.
A person’s blood type is determined by the presence of antigens on the surface of the red blood cells in their body. Type A blood has the A antigen, B has the B antigen, AB has both and O has none, the study published in Science Translational Medicine explains.
Because Antigens A and B are present on the surface of blood vessels in the body, including vessels in solid organs, an organ would likely be rejected if given to someone with a different blood type than them.
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“If I have someone that is very sick and for example is an O blood type and they get a B or A donor offer for transplantation, I cannot transplant that patient,” Dr. Cypel said. “That patient may die before the next organ is available for him or for her.”
Patients with type O blood wait on average twice as long to receive a lung transplant compared to patients who are type A, according to Dr. Aizhou Wang, a scientific associate working with Dr. Cypel. This means patients who are type O have a 20 per cent higher risk of dying while waiting to be matched.
A patient who is type O or B and in need of a kidney transplant will wait an average of four to five years, compared to two to three for types A or AB.
In Ontario alone, there are currently around 1,600 people waiting for a life-saving organ transplant, according to the Trillium Gift of Life Network.
“In this way, every donor that we get, we could transplant based on which recipient is the sickest one and not have these separate lists,” Dr. Cypel said of the study’s findings.
To test if this type of treatment would work, Dr. Cypel and his team conducted an experiment on human lungs at his lab — part of the Latner Thoracic Surgery Research Laboratories.
The lungs chosen were not suitable for transplantation from type A donors. They were put into a Toronto-made system called the Ex Vivo Lung Perfusion System (EVLP) for treatment.
In order to clear the antigens from the surface of the organ and make it universally useful, the team treated one of the lungs with a group of enzymes found in 2018 by a professor of biochemistry at the University of British Columbia, Dr. Stephen Withers, along with his team. The other lung remained untreated.
“The enzymes themselves are ones that we discovered by hunting within the human gut microbiome,” Dr. Withers said, noting he’s been broadly working on this class of enzymes for 30 years.
Although the team was initially aiming to develop a method to improve the supply of O-type universal donor blood, they also realized there was a potential for application in organ transplantation but didn’t have the data on it until they began working with Dr. Cypel.
Once the lungs were treated with the enzyme, the team tested them by adding type O blood to the ELVP System to mimic an incompatible transplant.
The treated lungs were well tolerated while the untreated ones showed signs of rejection, meaning the experiment worked.
This study could not only change the landscape for lung transplants but also for other organs as well, according to Dr. Cypel.
“This can be used for any organ,” he said. “There is no reason to think that that this wouldn’t work by prefusing kidneys, livers or hearts, for example.”
At this stage, the work is being funded from a grant written more than three years ago in conjunction with the doctors involved, Dr. Withers said.
How could this impact transplant patients?
Elizabeth Ostrander, a 57-year-old from St. Catharines, Ont., waited for a lung transplant for two years after being diagnosed with COPD (chronic obstructive pulmonary disease). One of the main reasons? Her B positive blood type.
“Everyday life was getting harder. Breathing was harder. Going up the stairs was very hard,” she told Global News.
In the centre where Dr. Cypel works, and where Ostrander is a patient, the average wait time for a lung transplant is three months.
“I was hopeful but there were times I thought they were never going to find a match,” she said. “I was getting a little bit frustrated and just depressed about not getting a match and possibly never getting it.”
After three unsuccessful attempts, a fourth call to the hospital for a potential match brought on an unfamiliar batch of nerves for Ostrander.
“Maybe that’s a positive sign that this is going to be the one,” her nurse told her.
So it was. On Nov. 13, 2021, Ostrander received her lung transplant – something she would’ve gotten much sooner had doctors been able to use donors outside of her blood type, Dr. Cypel said.
Waking up to see her husband after surgery was “amazing” for Ostrander. However, waiting so long for the transplant took important time away from her.
“I missed out on a lot because of waiting so long,” she said. “I would have been able to do more with my family.”
Now, three months into recovery, Ostrander says the study will be a game-changer for the future of transplant patients.
The team is “optimistic” about clinical trials, according to Dr. Wang.
The first clinical trials could happen within the next 12 to 18 months, according to Dr. Cypel.
“The main feature now for us to be able to do this is for the company that is producing this enzyme to get all the approvals from a production standpoint,” he said.
For clinical trials, type A donors that have lower A antigen expression will be used but all types would be used in the future.
Any clinical studies, including this one, will go through a process that is filed to the hospital’s research ethics board to be processed and assessed, said Ana Fernandaz, spokesperson at the University Health Network.
Meanwhile, Dr. Withers is “stoked” to hear how quickly things could move to trials.
“We’re happy this work is proceeding forward,” he said.