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UIC tests diabetes drug in treatment of multiple sclerosis

08.06.2004


Researchers at the University of Illinois at Chicago are launching a clinical trial to determine whether a drug commonly used for diabetes might be effective in treating multiple sclerosis, an autoimmune disease that affects 350,000 Americans.



In an animal model of the disease, the researchers found that the drug reduced the inflammation of nervous tissue that occurs with multiple sclerosis and prevented the aberrant immune response that ends up destroying the body’s own brain and spinal cord.

"At present, few medications have been approved by the Food and Drug Administration for the treatment of multiple sclerosis," said Douglas Feinstein, associate professor of anesthesiology in the UIC College of Medicine. "These drugs are only partially effective, and none helps significantly in the later, progressive forms of the disease. The drugs also have undesirable side effects, and they need to be injected, making them difficult to administer."


The drug being tested, called pioglitazone, is prescribed for the treatment of type 2 diabetes. Marketed by Takeda Pharmaceuticals North America, pioglitazone "sensitizes" the body’s cells to insulin, a hormone produced by the pancreas that lets sugar into cells so that it can be converted into energy. People with type 2 diabetes are unable to use insulin efficiently, leading to elevated blood sugar levels (hyperglycemia) and tissue damage.

Research has shown that drugs like pioglitazone not only raise the levels of certain proteins involved in the uptake and metabolism of glucose but also lower the levels of other molecules involved in the immune response and inflammation.

"It is amazing that this drug, at least in animal tests, has shown a dramatic effect on two different targets of multiple sclerosis, namely the immune system and the inflammation process," Feinstein said.

Feinstein also noted that the drug is available as a tablet, simplifying its administration.

The clinical trial will enroll about 30 patients with relapsing remitting multiple sclerosis, the most common form of the disease. People with this type of multiple sclerosis experience episodes of acute worsening of neurological function, followed by partial or complete recovery. In most patients, the disease will eventually change into a chronic, persistent form, with symptoms worsening throughout life.

Participants in the trial will take a 30-milligram dose of pioglitazone daily for a period of 18 months, during which they will be monitored for any side effects or changes in their symptoms.

"At this stage in the drug trial, we are simply trying to determine whether the drug is safe and can be tolerated by people with multiple sclerosis," Feinstein said. "But we’ll also be doing neurological examinations and biochemical analyses of blood samples, looking for signs of inflammation and immune cell activation to determine whether the drug is having any effect on symptoms of the disease."

Employing UIC’s state-of-the-art magnetic resonance imaging technology, the researchers will do a series of three brain scans over the course of the trial to look for changes in the cerebral lesions associated with multiple sclerosis.

In multiple sclerosis, the T cells of the immune system go awry, attacking proteins in the myelin sheath that insulates the nerve fibers. When the sheath is destroyed, electrical signals that are normally transmitted throughout the brain and spinal cord are disrupted, and the brain is no longer able to correctly send or receive the messages that help control muscle movements.

Patients with multiple sclerosis suffer a range of symptoms, including tingling and numbness, loss of balance, blurry vision, weakness in the limbs, difficulty walking, impaired thinking and even paralysis. The disease affects women about twice as often as men.

In the United States, health care costs for multiple sclerosis are second only to those for Alzheimer’s disease.


Co-directors of the UIC study are Drs. Daniel Hier and Demetrios Skias, in the department of neurology at UIC, and Dr. Dusan Stefoskil, director of the multiple sclerosis clinic at Rush University Medical Center.

The study is funded by Takeda Pharmaceuticals North America, Inc.

Sharon Butler | EurekAlert!
Further information:
http://www.uic.edu/depts/mcam/

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