Vaccine Reverses Type 1 Diabetes in Mice
THURSDAY April 8, 2010 -- Canadian researchers have successfully reversed type 1 diabetes in mice using a new vaccine technology that appears to solely target the immune system cells responsible for the disease.
"The body has built-in mechanisms that try to counter disease progression, and we now have a mechanism that can be [used] to selectively blunt an immune response without causing a systemic response," said the study's senior author, Dr. Pere Santamaria, a professor at the Julia McFarlane Diabetes Research Centre at the University of Calgary in Alberta.
What's more, Santamaria said, the technique developed for the diabetes vaccine may be applicable to other autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis.
So far, the research has only been conducted in mice. "We don't yet know if it will work in humans, but we're very excited and think this offers hope," said Santamaria.
Type 1 diabetes is an autoimmune disease. That means that the body's immune system, which usually targets invading unwanted cells, such as bacteria, mistakenly destroys healthy cells. In the case of type 1 diabetes, the immune system destroys the insulin-producing beta cells in the pancreas. This knocks out the body's ability to produce insulin, the hormone that helps convert blood sugar to energy for cells in the body. So, people with type 1 diabetes must inject insulin multiple times a day, every day, to stay alive.
"Autoimmune diseases, like type 1 diabetes, multiple sclerosis and rheumatoid arthritis, are caused by an overactive immune system. Normally, the immune system helps us fend off cancer and infection, but in some people, it becomes overaggressive," Santamaria explained.
Although there are medications available that can dampen the entire immune response, these medications can create additional problems, such as an increased risk of cancer and serious infection.
However, the Canadian researchers discovered that the body doesn't just allow the autoimmune aggression to go unchecked. There is a counter-mechanism that produces immune system cells to try to fight the rogue immune cells that are creating the damage in type 1 diabetes.
But these cells -- know as memory-like autoregulatory T cells -- aren't as strong as the rogue cells and so they quickly become overwhelmed.
Using a "nanotechnology-based" vaccine, the researchers were able to boost the effects of the weaker immune cells, which allowed them to stop the damaging immune cells from attacking. The vaccine consists of nanoparticles -- spheres thousands of times smaller than a single cell of the body -- "coated" with antigens that bind to molecules used to stimulate certain T cells.
"With this nanovaccine, we engage the weak immune cells and make them multiply and divide, and then they can counter the autoimmune response without impairing systemic immunity," said Santamaria.
Instead of directly attacking the stronger cells, the autoregulatory T cells turn off the signal that tells the stronger immune cells to attack, effectively stopping the destruction of the beta cells.
Santamaria said it's not clear yet if this vaccine would be a one-time treatment, or would need to be administered periodically. He said it's likely additional treatment might be necessary.
Santamaria said the next step in his work is to produce the drug in a version that can be used in clinical trials on humans.
Teodora Staeva, director of Immune Therapies for the Juvenile Diabetes Research Foundation International, called the new research "a very novel therapeutic approach that seems to have great potential."
"A lot of work remains to be done. This therapy has the promise of being safer -- although that has to be proven in toxicology studies -- because it specifically targets the cells that are causing the problems," Staeva said.
Staeva said that if this vaccine proves itself in human studies, it has the potential to help both newly diagnosed type 1 diabetics and those who've had the disease for years. But, she said, in people who've had type 1 for a long time, beta cell transplantation might be necessary.
Results of the study were published online April 8 and are to appear in the April 23 print version of the journal Immunity.
Learn more about type 1 diabetes and the role of the immune system from the Juvenile Diabetes Research Foundation.
Posted: April 2010
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