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Two Cancer Drugs Show Promise For Preventing and Reversing Type 1 Diabetes

Researchers at the University of California, San Francisco have reported that two common cancer drugs have been used to block and reverse type 1 diabetes.

“The findings suggest that kinase inhibitors – successfully used in cancer – may provide an important new therapeutic approach for treatment of new onset type 1 diabetes and potentially other autoimmune disorders,” said JDRF Director of Immunology Teodora Staeva, Ph.D.

The drugs – Imatinib and Sunitnib, sold as Gleevec and Sutent, respectively – are used to treat cancer by blocking tyrosine kinases, an enzyme that modify cells’ signaling proteins through a simple biochemical change. Kinases trigger cell growth, and it is widely believed that tyrosine kinases are a contributing factor to autoimmune diseases and cancer. The researchers hypothesized that tyrosine kinases may also serve as a trigger to the body’s attack on the immune system.

“There are very few drugs to treat type 1 diabetes, especially after disease onset, so this benefit, with a drug already proven to be safe and effective in cancer patients, is very promising,” Jeffrey Bluestone of the University of California, San Francisco, said in a statement.

“The fact that the treated mice maintained normal blood glucose levels for some time after the drug treatment was stopped suggests that imatinib and sunitinib may be ‘reprogramming’ their immune systems in a permanent way,” said Bluestone.
Type-1 diabetes affects an estimated 5 to 10 percent of the 20 million Americans with diabetes. Also called juvenile diabetes, it has different causes from the more common type-2 diabetes that is linked with obesity, poor diet and a lack of exercise. Type 1 diabetes is an autoimmune disease caused by the destruction of insulin-producing cells in the pancreas.
Both Gleevec and Sutent inhibit tyrosine kinases, enzymes that are needed for cell communication and growth and are linked with inflammation and immunity.

Bluestone and colleagues wondered if these drugs could block some of the same tyrosine kinases involved in the development of type 1 diabetes.

They tested the drugs in mice predisposed to type 1 diabetes and found that the drugs kept the mice from developing diabetes.

They also tested them in mice with the disease and showed the drugs put the disease in remission in 80 percent of the animals after only eight to 10 weeks of treatment.

They said the drugs appear to block receptors of a tyrosine kinase not known to be involved in diabetes. This enzyme, known as platelet-derived growth factor receptor, or PDGFR, regulates cell growth and division, and also plays a key role in inflammation.

“This study opens up a new area of research in the field of type 1 diabetes, and importantly, opens up exciting opportunities for developing new therapies to treat this disease and other autoimmune diseases,” Dr. Arthur Weiss of University of California, San Francisco, who worked on the research, said in a statement.

The JDRF-funded study,was led by Jeffrey Bluestone, Ph.D., director of the Diabetes Center at UCSF and an expert in the field of autoimmunity.

The Proceedings of the National Academy of Sciences, Nov, 2008