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Vaccine May Slow Progress of Diabetes

By Shari Roan
LA Times Staff Writer

July 14, 2003

If Daniel Kaufman hadn't had car trouble, he might have missed the biggest discovery of his career.

As a young neuroscience researcher at UC San Diego's Salk Institute in the early '90s, Kaufman left for home one day only to find that his car wouldn't start.

He tried to return to his lab while awaiting a ride but found the floor was being waxed. He then wandered into the institute's library and picked up a medical journal. It fell open to an article on Type 1 diabetes.

Kaufman knew that a particular brain protein he had been studying also was released in the
pancreas - in the cells that secrete insulin. He suddenly realized that the protein might playa
role in the development of Type 1 diabetes. “The light bulb went off, " he says.

In Type I diabetes, which typically starts in childhood, the immune system attacks the pancreas' insulin-producing cells. Over time, this reduces insulin, the hormone that controls blood-sugar levels. Type I diabetics must have daily insulin injections so glucose can be transported to cells and produce energy.

Kaufman soon joined researchers Allan Tobin and Jide Tian at UCLA to further study the protein, called GAD. The team believed that the development of diabetes could be caused by the immune system attacking the GAD protein in insulin-producing cells. In a study published in Nature in 1993, they showed that giving young diabetes-prone mice small amounts of GAD taught the mice's immune systems to recognize GAD and not attack the protein as a foreign substance. The mice did not develop the autoimmune response that leads to diabetes.

In 1996, the team showed that a vaccine could inhibit the autoimmune response after insulin- producing cells already were under attack.

"This vaccine is based on injecting the very protein that is being attacked,” Kaufman says. But instead of boosting the attack, it is meant to activate cells that release calming substances.”

UCLA eventually licensed the technology to a Swedish company, Diamyd Medical, to develop and test the vaccine in humans. In a study presented last month at the American Diabetes Assn. convention, researchers showed that the
vaccine was safe and prolonged the ability of the pancreas to make insulin in adults recently diagnosed with late-onset
Type 1 diabetes.

Type 1 diabetes takes years to develop and symptoms often emerge only after insulin-producing cells are extensively
damaged. Researchers hope, however, that giving the vaccine to children as early as possible in the onset of the disease will help prolong their ability to make insulin. Future studies will address that question.

Kaufman's research also has produced a diagnostic test that indicates who is at risk for developing diabetes. With early diagnosis and the vaccine, the ultimate goal is to prevent the disorder from developing.

"Since it worked on people with very late stages of the disease process, we're optimistic that even better efficacy will be found in young people who don't have the full onset of the disease," Kaufman says. And it proves that sometimes car trouble isn't so bad.

Type 1 diabetes often is referred to as juvenile diabetes because it most often occurs in childhood; the average age of onset is 12. However, the disease can occur at any age. Symptoms include increased thirst and urination, hunger, unexplained weight loss and fatigue.

This form of diabetes results from the body fighting itself in a so-called autoimmune attack that causes the pancreas to produce little or no insulin. People with Type 1 diabetes must monitor their blood sugar levels and inject insulin daily. About 1.7 million Americans have Type 1 diabetes. (In Type 2 diabetes, the pancreas continues to manufacture insulin, but the body develops resistance to its effects. Obesity is a major risk factor for developing Type 2 diabetes, which usually begins in adulthood.)

There is no cure for Type 1 diabetes. Controlling blood sugar levels is important to avoid further complications, including heart disease, kidney failure and damage to the retina.

Original source: LA Times


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