University Of Alberta Research Team Is On The Cusp Of A Cure For Diabetes

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University of Alberta research team says the cure for diabetes is right around the corner

In the summer of 2000, a global spotlight shone on Edmonton, where University of Alberta scientists transformed the city into the world's leading light in the quest to cure Type 1 diabetes. A small team of researchers had done what until then had been impossible, helping patients with Type 1 diabetes become insulin-independent at an unprecedented success rate of 100 per cent. Termed the "Edmonton Protocol," the procedure became a ray of hope for those suffering from diabetes worldwide.

The foundations of the Edmonton Protocol were built through the pioneering work of Ray Rajotte, a professor of surgery at the University of Alberta and the founder of its Islet Transplant Group. In 1972 Rajotte attended a lecture by American researcher Paul Lacey, who had cured diabetic rats by transplanting the islet cells of healthy rats into them. In that moment, Rajotte saw a new path for his work in the isolation and cryopreservation of islet cells, with the hope it might one day have application in humans.

Over the next several years, Rajotte spent his time in research labs scattered across the United States learning all he could about isolating islets. In 1979, he returned to the U of A to join the departments of surgery and medicine, and began working toward moving his efforts from animal to human islets.

Together, the team hypothesized that if donor islets could somehow be isolated, they could be injected into the liver. There, they would become revascularized and perform their duties as usual, away from the besieged pancreas, where a diabetic's immune system inexplicably attacks healthy islets. With any luck, such a transplant-accompanied by a proper anti-rejection drug regimen-could allow a Type 1 diabetic to be free of insulin injections.

By the late 1980s, Rajotte's team felt it was finally ready for the next step-a clinical trial of human islets. In 1989, the group carried out Canada's first islet transplant.

"The first patient we transplanted, his insulin requirement went down, but he didn't quite get off insulin," says Rajotte. "The same thing happened in a second patient."

For a third patient, the team adjusted their methods, doubling the number of islets being injected and using a mixture of fresh and cryopreserved islet cells. This time, the patient achieved insulin independence for two and a half years.

"In all we did five islet transplants," says Norman Kneteman, '78 MD, '85 MSc, now director of the Division of Transplantation Surgery at the U of A. "Among those five we had two patients that we managed to get off insulin for extended periods of time. Those were some of the first in the world to achieve insulin independence … but the success that we had was not prolonged."

Unfortunately, islet cell implantation had major limitations. Transplant recipients are forced to take immunosuppressant anti-rejection drugs that come with a long list of side effects: Organ donations,  high blood pressure and increased risk of infections.

"Worldwide there were probably about 260 transplants carried out and only eight per cent of the patients got off of insulin," adds Rajotte. "Eight per cent just wasn't good enough."

They needed to go back to the drawing board.

Members of the Clinical Islet Transplant Program.Top, from left: Greg Korbutt, Eddie Ryan and James Shapiro.
Bottom, from left: Jonathan Lakey and Ray Rajotte

Fast Forward

Now, twenty years later, they're at it again. The team, led by Dr. James Shapiro, has been able to consistently cure diabetes in mice and is now looking to move to human trials.

Dr. James Shapiro and his university research team  report that they’ve been able to cure diabetes in mice. The team is using a technique that involves stem cells developing into pancreatic cells that can produce insulin. They believe their research will result in a functional human cure for diabetes.

“We’ve been working with a company called ViaCyte in San Diego for the last, almost 19 years now, and this company has a cell that is derived from a human embryonic stem cell that makes human insulin in a regulated, perfect way,” Dr. Shapiro said. “We’ve been able to treat countless thousands of mice with these stem cells and effectively cure mice with diabetes over many years now.”

The stem cell therapy that Dr. Shapiro is proposing has none of these drawbacks of islet cell implantation. The University of Alberta team foresee a one-time injection — with possible re-ups later on — of insulin-producing cells derived from human stem cells. No need for immunosuppressants or organ donations.

Close to a cure for Type 1 ...Type 2 is right behind

The researchers say they are closer than ever to a cure-and it's no longer just a cure for Type 1 diabetes they've got their sights set on. If they can break the code to avoid the need for anti-rejection drugs altogether, it would finally open the door to also treating patients with Type 2 diabetes-a population that makes up more than 90 per cent of all people living with diabetes.

While the path to a cure will still be filled with bumps, potholes and detours, U of A scientists and clinicians continue to forge ahead. At the Alberta Diabetes Institute-the largest organization of its kind in North America-about 40 scientists with support staff and graduate students numbering more than 300 are working on finding a better treatment or cure, says Rajotte.

"The U of A and the clinical islet program are still the world's epicentre for the therapy and are at the cutting edge of clinical trials," says Andrew Pepper, PhD, an assistant professor of surgery at the U of A. "We're moving research from the lab into patients and are doing so at the very highest of standards," said Pepper.

"There are no other centres in the world doing what we are doing today," adds Shapiro. "This work is like a big puzzle and right now the pieces seem to be scattered. But the picture is coming into place."

Nearly 100 Years Since Banting and Best

2022 will be the 100th anniversary of the first successful insulin injection. In 1922, Dr. Frederick Banting and his small team, working out of the University of Toronto, saved the life of a 14-year-old-boy named Leonard Thompson, who was dying from diabetes.

You're basically Back-To-Normal

When Dr. Shapiro was asked at what point he would consider it a cure for diabetes, he said: "This will be a cure when we have cell-based treatment that we put into a patient, it's either a one-off treatment, or maybe it needs to be topped-up over time, and that's it, done and dusted. You don't need to take anti-rejection drugs, the cells continue to work, you don't need any insulin, you don't have to monitor yourself, you don't need regular blood checks. You're basically back to normal."

Donate To This Amazing Research  - Help Make It Happen

Shapiro's team is now ready to move on to human trials. The biggest obstacle is money. The group wants to raise $22 million by 2022 to help bring Dr. Shapiro’s new treatment to the next phase of trials.

"We want to turn diabetes into a disease that is like the common cold; it came and it went."

If one million people (diabetics or otherwise) donate $22 today and encourage their friends and family to do the same, the cure for diabetes is within sight. 

Dr James Shapiro provides a research update, November 2018

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