A World First in Diabetes Treatment
A World First in Diabetes Treatment
Summer 2000
They’re not brand spanking new or state-of-the-art. In fact, they’re in the basement and don’t even have windows.
But the labs and offices of the principal researchers involved in developing the now-famous “Edmonton Protocol” diabetes treatment have a pedigree that seemed to foreshadow the phenomenal research success of its current occupants. Eighty years ago, this same basement area was the research laboratory of Dr. James Collip, a major Canadian scientific figure who made significant contributions to the discovery of insulin.
Dr. Jonathan Lakey and Dr. Greg Korbutt are proud of the Collip connection, but they attribute the 100% success rate of their new treatment to perseverance and vision rather than coincidence. Both Heritage researchers were protégés of Dr. Raymond Rajotte, the Director of the Islet Cell Transplant Group and leader of the Edmonton Protocol research group. Dr. Korbutt, the Director of Quality Control for the Islet Cell Transplant Group, first worked with Dr. Rajotte as a NAIT graduate in biological sciences. Dr. Rajotte motivated him to first pursue his doctorate and then obtain specialized training in characterizing islet cells.
Dr. Lakey met Dr. Rajotte while he was finishing his master’s degree in physiology. He completed his doctorate and post-doctoral fellowship with Dr. Rajotte and Dr. Garth Warnock before going to the Cryobiology Research Institute in Indianapolis for training in low-temperature biology. He is now the Director of the Human Islet Isolation Laboratory, which isolates the human islets for clinical transplantation.
Together with Dr. Rajotte and the other clinical and basic researchers on the team, the two scientists worked on refining the pioneering work in islet-cell transplantation done in 1989 by Dr. Rajotte, Dr. Warnock, and Dr. Norm Kneteman. Islet cells were transplanted into the diabetic patient’s liver in the hope that the cells would take hold and produce insulin. However, the initial transplantations had only an 8% success rate. Within a few months, all the patients had to go back to injecting insulin.
So what made the group persevere with, in their own words, such a “dismal failure rate”? Dr. Lakey and Dr. Korbutt give credit to Dr. Rajotte’s vision: “He knew the idea could work. But he also knew no one person could have the expertise needed for such a complex procedure. So he strategized for the future. He sent people all over the world to get specialized training. Then he brought them together and built a total team.”
The total team approach worked because each member came in with new knowledge that led to a number of innovative changes in the transplantation procedure. The result revolutionized diabetes treatment.
By June 2000, a total of eight Alberta patients had received Edmonton Protocol transplants of islet cells. They were all severely diabetic, many of them suffering from “brittle diabetes”, a form of the disease that causes unexpected and dangerous fluctuations in sugar levels. All eight patients have become insulin-independent—a first in world history—one of them for as long as 16 months.
What’s in the future? More research, according to Drs. Korbutt and Lakey. “We know that the pancreas has a branching system of ducts that are precursors to islet cells. If we can take this tissue and grow islet cells, we could transplant two, maybe five or more people from one donor,” says Dr. Lakey.
“Islet cells aren’t just one type of cell, but a ‘stew’ of many cells. We now know exactly what we are putting in along with the islets, whether it’s insulin-secreting cells or ductal cells,” says Dr. Korbutt. “But we want to determine exactly how those cells are contributing to the production of insulin.”
Public awareness of the prevalence and severity of diabetes is important too. Dr. Lakey points out: “This treatment means some Type I diabetics are free from insulin injections and from progression of the disease. But at this point it isn’t for everyone with diabetes, and it isn’t a cure.”
Both researchers comment, “There are another 40 people waiting in Alberta who fit the criteria for transplantation. We receive hundreds of phone calls and e-mails a day from all over the world. The availability of organs is crucial. If everyone filled out their donor cards, we could help a significantly greater number of patients.”
“Given that about 15% of healthcare dollars goes to treatment for diabetes and its complications, we want to see this therapy improved so that it can be offered to all types of diabetics.”
Dr. Jonathan Lakey and Dr. Greg Korbutt are AHFMR Scholars, and Assistant Professors in the Faculty of Medicine at the University of Alberta. Dr. Korbutt also receives funding from the Canadian Diabetes Association; Dr. Lakey, from the Edmonton Civic Employees. Drs. Korbutt and Lakey receive support from the Canadian Institutes of Health Research, formerly the Medical Research Council of Canada, and the Juvenile Diabetes Association International. The funding for human trials was provided by the Alberta Foundation for Diabetic Research.
AHFMR has provided approximately $20 million in funding support for diabetic research at the University of Alberta over the past 20 years. Dr. Rajotte received some of the first funding from AHFMR in 1980. AHFMR currently funds or has funded nearly all the members of the Edmonton Protocol diabetes team.
The Clinical Islet Transplant team and affiliated researchers: Dr. Ray Rajotte, Dr. James Shapiro, Dr. Edmond Ryan, Dr. Jonathan Lakey, Dr. Greg Korbutt, Dr. Tim Kieffer, Dr. Alex Rabinovitch, Dr. Allan Murray, Dr. John Elliott, Dr. Chris Bleackley, Dr. Norm Kneteman, Dr. Garth Warnock, Dr. Ron Moore, as well as many students, post-doctoral fellows, and a dedicated group of technicians.
Diabetes Facts
Diabetes is a chronic, genetically determined, debilitating disease affecting many organ systems. It is the leading cause of kidney failure, adult blindness, and non-traumatic amputations, as well as a major cause of nerve damage. Life expectancy of people with Type I diabetes averages 15 years less than people without it. Life expectancy of people with Type II diabetes is shortened by 5 to 10 years. The disease is enormously costly to the healthcare system.
There are two major types of diabetes: Type I and Type II. Type I, previously called juvenile-onset diabetes, is caused by the autoimmune destruction of the insulin-producing cells in the pancreas and is usually, though not always, diagnosed in childhood. It is also known as insulin-dependent diabetes, for people with Type I diabetes must take insulin to live. People with Type II produce insulin, but their bodies do not use it effectively. Type II is usually diagnosed in adulthood, can be controlled with exercise, diet, and oral drugs, and does not always require insulin injections.
Courtesy of the University of Alberta, Faculty of Medicine
