In the Footsteps of History
While on sabbatical from the University of Alberta (U of A) in 1922, biochemist J. B. Collip isolated a pancreatic extract that was pure enough to use in clinical trials. Credited as a co-discoverer of insulin, Collip pursued his pioneering work in endocrine research at a basement laboratory at the U of A.
That same laboratory was the heart of biochemical research for the Edmonton Protocol, a method of isolating and transplanting human pancreatic cells, in the 1990s. Early human islet recipients with type 1 diabetes remained insulin-free for up to a year after transplantation.
During that era, Gregory Korbutt, a promising young technician and recent graduate of the Northern Alberta Institute of Technology (NAIT), began work at the laboratory under the leadership of Dr. Ray Rajotte, founder of the Islet Transplantation Group (ITG).
“After that first year of working with Ray, I decided I wanted to be more than a laboratory technician,” says Dr. Korbutt. He enrolled in undergraduate and graduate programs at the U of A, working at the laboratory in summers. He pursued his PhD studies in Belgium, returning to Edmonton to complete a post-doctoral fellowship. He became a member of the original Edmonton Protocol team and, today, works with colleagues in transplantation research at the Alberta Diabetes Institute.
Finding alternatives for islet transplantation
Dr. Korbutt’s groundbreaking research has advanced the field of islet transplantation even closer to a cure for diabetes.
In the 1990s, he joined the search for alternatives to human pancreatic islets, which were in short supply for transplantation due to a lack of human donors. Many scientists had studied the use of pancreatic islet cells from adult pigs, but those cells were extremely fragile. Out of the blue, Dr. Korbutt decided to investigate the use of pancreatic islet cells from neonatal pigs.
“That’s how research works. You just think, okay, I’ll try that, and sometimes, it happens,” he says. “You’re trying to discover new ways to do things. Usually, it doesn’t work as well as you want, but when it does, it’s a real thrill.”
He developed a protocol for reliably isolating large numbers of viable cells from this source. With his U of A colleagues, he published the seminal paper, “Large-scale isolation, growth, and function of porcine neonatal islet cells” in the prestigious Journal of Clinical Investigation in 1996.
Since this discovery, Dr. Korbutt and his collaborators in Edmonton and, later, Atlanta, have successfully transplanted islet cells from neonatal pigs into progressively complex animal models – mice, adult pigs and monkeys – and cured diabetes.
Safe cells for diabetes research
“Whenever I give a talk to families of children with type 1 diabetes, that inspires me a lot,” says Dr. Korbutt. “That wakes you up and reminds you why you’re doing this research.”
Dr. Korbutt and his colleagues are now gearing up to transplant neonatal pig islet cells into humans, but before that can happen, the Alberta Diabetes Institute needs to build a Good Manufacturing Processes (GMP) facility to produce enough neonatal pig islets of consistent quality for use in clinical trials.
He has won $26 million in grants from the Canadian Foundation for Innovation, Alberta government, and University of Alberta to fund construction in Edmonton of a world-class GMP facility to process the islets and more. It’s the first laboratory of this quality in Western Canada and one of four in the country. When it is built, Dr. Korbutt will become Scientific Director of the new facility.
Clinical trials of neonatal pig islet transplantation may begin as early as 2013, Dr. Korbutt believes. The first recipients are likely to be people with brittle diabetes or people with diabetes and kidney transplantations. The latter are more prone to rejecting human islets due to conflicts with immune-system antigens, he says.
Next steps: stem cell research
The Cell and Tissue Innovative Research Centre, scheduled to open in late 2012, will contain five laboratories for human stem-cell research. One of these laboratories will be devoted to diabetes research, as the next step in Dr. Korbutt’s relentless search for a cure.
There are many benefits to studying human stem cells, he says. Scientists have found that stem cells extracted from a patient’s bone marrow, then multiplied, can be co-transplanted with islet cells in patients with diabetes to prevent rejection – the most common hurdle to overcome in transplantation.
“We envision the neonatal pig islets as a short-term solution, whereas the human islet stem cells will be the longer solution,” he says.
For further information, please contact Greff Korbutt using the Email contact form
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