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Tests of an experimental drug called CPSI-1306 at Ohio State University were so successful at lowering inflammation and blood sugar levels in lab mice with type 2 diabetes that scientists consider it a prime candidate to become a new therapy for the disease.
CPSI-1306, a synthetic molecule manufactured by Pennsylvania-based Cytokine PharmaSciences, Inc., stops a protein called MIF (macrophage migration inhibitory factor), which is a known cause of inflammation in several diseases.
Before the OSU scientists began experimenting with the drug, they wanted to see how mice genetically bred to lack MIF responded to induced type 2 diabetes. So they used a toxin called streptozotocin, which kills pancreatic beta cells, to induce diabetes in normal mice that had MIF and in the mice that lacked MIF.
Once both sets of mice had acquired type 2, the researchers tracked them to see how their bodies would behave with the disease. The normal mice with MIF showed a continual rise in blood sugar levels, as well as increased appetite, excessive urine, and weight loss-classic symptoms of the onset of type 2.
However, the mice lacking MIF experienced little weight loss and showed a drop in blood sugar after seven weeks. In glucose tolerance tests, their blood sugar levels decreased faster than they did in the diabetic mice with MIF. This proved that MIF is a significant contributor to the effects of diabetes.
After the tests with the two groups of lab mice, the scientists induced type 2 in a third group of normal mice that had the MIF protein. Once the mice had the disease, researchers began treating them daily with orally administered doses of CPSI-1306. After 30 days of treatment with the drug, the mice were recording blood sugar levels below 200 milligrams per deciliter, roughly equivalent to an A1c reading of 8%. Untreated diabetic mice exceeded 400 milligrams per deciliter-an A1c reading of about 14%.
The OSU researchers followed that result by testing blood samples from people with type 2 and people without diabetes. They found that people with type 2 had what they described as "significantly higher levels" of MIF in their blood, as well as two chemical messengers known to cause inflammation: interleukin-6 and tumor necrosis factor-alpha.
The successful lab experiment with CPSI-1306 opens the door for a type 2 drug treatment that heads in a different direction. Most type 2 therapies either stimulate the body to increase insulin production or to become more sensitive to the insulin that it does produce-sometimes both. A drug based on CPSI-1306 would lower inflammation and lower blood sugar levels by controlling MIF, without the need to stimulate more insulin production.
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OSU press release
0 comments - Apr 8, 2010
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