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Canadian Solves Diabetes Mystery-Calgary Scientist's Discovery Raises New Hope For Child Sufferers

Editor's Note: Editor's Note: The following is re-printed from the Globe and Mail, May 14, 1999.

A Calgary scientist has finally cracked the mystery of how children get diabetes, a breakthrough that holds out hope for the first time that they could be vaccinated against it.

Ji-Won Yoon, an immunologist and virologist at the University of Calgary, discovered that the clue to the baffling Type 1 diabetes, which children and young adults develop, lies in an enzyme produced in cells in the pancreas. It's called the glutamic acid decarboxylase (GAD).

Dr. Yoon conducted his research on mice but said in an interview that the trigger for the disease is the same in mice and humans and that he is poised to start clinical trials on humans. His landmark findings are to be published today in the Journal of Science.

Dr. Yoon's research was spawned by the puzzling fact that children who develop diabetes also have the unusual antibody to GAD in their blood. In fact, the presence of the GAD antibody is one of the ways doctors diagnose diabetes in the young. Dr. Yoon theorised that a child who develops diabetes also has an off-kilter immune system that allows the body's infection-fighting T-cells to attack the GAD enzyme when they should not. That harms the pancreas and destroys the body's ability to produce enough insulin. Insulin is the hormone that allows the body's cells to convert sugar to energy. The lack of insulin results in Type 1 diabetes, a condition that attacks children and young adults, normally setting in at around the age of ten. So what Dr. Yoon did was to genetically alter some diabetes-prone mice. In half the mice, the GAD enzyme was present; while in the others, it was suppressed. His study showed that when GAD was absent, the mice did not develop the disease.

The enormous implication of the finding is that if doctors could vaccinate new-borns with GAD, that would build up a tolerance for it among the T-cells and prevent them from destroying GAD-and the insulin-producing cells of the pancreas-later on. And that could prevent children from developing diabetes.

Dr. Yoon compared the possible development of a vaccine to the family dog that grows accustomed to the children of the house and doesn't attack them. A vaccine would essentially train the immune system not to destroy the GAD enzymes. Dr. Yoon said in an interview that in years to come, as this technique is better developed, the most likely new-borns to be routinely vaccinated would be those with a family history of Type 1 diabetes. But he said eventually every new-born could be inoculated against the disease.

The find has radically altered the way doctors understand the childhood version of the disease. Dr. David Lau, a doctor and biochemist at the University of Ottawa who will shortly take over as director of U of C's Julia McFarlane Diabetes Research Centre, said that until now, researchers knew the GAD antibody was present in those with Type 1 diabetes but did not understand its link with the disease. He called Dr. Yoon's work "ingenious." "I think it has important therapeutic implications in future," Dr. Lau said. However, he added: "It's not necessarily a cure at the moment."

Dr. Lau said he thinks applications for humans could be "a few" years away. He said the find is especially important because both the number of cases of diabetes and the rate at which the disease affects the population are rising across the world. Dr. Yoon, U of C's Julia McFarlane Chair in Diabetes Research and a diabetes researcher for 25 years, said the next step is to launch clinical trials which await some bureaucratic approvals. He has already developed the human vaccine.

Dr. Yoon said the find has no implications for people who have Type 2 diabetes, which usually occurs in adults. Type 2 diabetes is caused not by an immune-system problem that destroys the body's ability to produce insulin, but rather by the body's inability to use the insulin it produces. About 10 per cent of those affected by diabetes have Type 1. About 1.5 million Canadians have been diagnosed with diabetes.

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