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Wayne State University researcher's model will target causes of everyday MS symptoms

Detroit Annoying, frustrating symptoms like difficulty hearing or remembering things can complicate everyday living for multiple sclerosis (MS) patients, but most research to date has focused on the disease's less frequent but more debilitating consequences.

Recently, however, an increasing number of patients have expressed their desire for a better quality of life between relapses, as the body attacks its own central nervous system, which can cause blindness or the inability to use a limb.

"Everyone reacts more strongly to changes that are big rather than subtle changes that occur every day," said Alexander Gow, Ph.D., professor in Wayne State University's Center for Molecular Medicine and Genetics and School of Medicine's departments of pediatrics and neurology, who recently received a one-year, $114,000 grant from the U.S. Department of Defense to develop a new model system that focuses on the latter.

Approximately 400,000 Americans have MS, and every week about 200 people are diagnosed. Worldwide, it affects about 2.5 million people.

Over time, Gow said, MS patients can lose their ability to focus mentally, forget what they want to do or have difficulty following conversations. But because the causes of MS are still somewhat unclear, he believes part of the reason for the lack of attention to such symptoms may lie in clinicians' inability to offer solutions to patients.

Patients can become extremely depressed or frustrated at their inability to perform daily mental functions, which has led some to undergo drug treatments similar to those used to treat behavioral disorders. However, Gow said, such treatments may not be all that effective for many MS patients.

He believes the immune system attacks that damage or destroy white matter brain cells (oligodendrocytes) and cause the more catastrophic symptoms of MS also destroy cells in the brain's gray matter cells (neurons), where auditory, visual and cognitive functions are based.

"Changes in gray matter could well be associated with emotional outbursts," Gow said. "Cells involved in memory and learning are also being destroyed. Whenever those sorts of changes occur, you almost always see frustration in patients as they try to grapple with the resultant loss in mental capacity.

"That causes them to be upset about not being able to do things, even if they don't know that's what's going on physically. This can also lead to them withdrawing from social settings with family and friends, which deepens the impact of MS."

MS patients' more severe symptoms result when the immune system attacks the myelin that surrounds white matter cells, causing lesions that are visible in magnetic resonance imaging scans. Myelin is a soft, white coating of nerve fibers composed of fats and protein that serves as insulation and as an aid to efficient nerve fiber conduction. When myelin is damaged in MS, nerve fiber conduction is faulty or absent, resulting in impaired bodily functions or altered sensations.

Gow said if viewed the right way, lesions also can be seen in gray matter, indicating that neurons and not just oligodendrocytes are being destroyed.

"That then gives us an anatomical basis for memory loss and patients' inability to focus," Gow said.

Because many brain pathways in Gow's model system are similar to those of humans, he is working to understand what happens when gray matter cells are destroyed as a consequence of the body's immune system. The grant will be used to look for more defined lesions in both white and gray matter when myelin is attacked.

Researchers then will look for behavioral changes similar to those seen in MS patients. They will examine white matter for specific changes indicating the presence of biomarker substances that cause MS-like symptoms. If those substances are found, researchers then can try to administer drugs to reverse the effects of the myelin attacks.

"Using different classes of existing drugs," Gow said, "novel therapies can be developed with shorter delays in moving from the bench to the bedside."

Treating MS patients with drugs used for typical behavioral disorders such as schizophrenia and depression can have terrible side effects for patients, he said, and can be ineffective because the drugs are attempting to rectify nonexistent imbalances in brain neurochemicals. If successful, Gow's research will provide a way to more accurately diagnose what is happening to MS patients, which could result in more effective treatments and improved quality of everyday life.


Contact: Julie O'Connor
Wayne State University - Office of the Vice President for Research

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