As reported by The Hartford Courant, October 25, 2005.

Telltale MS Markers

By William Hathaway

Some secrets of multiple sclerosis, a disease that afflicts between 250,000 and 300,000 Americans, have remained remarkably resistant to scientific inquiry.

While new magnetic resonance imaging technologies have allowed doctors to spot the disease's telltale central nervous system lesions, doctors still can't tell newly diagnosed patients whether the course of the autoimmune disease will be relatively benign or life-threatening.

"It's frustrating for patients,'' says Dr. Michael Carrithers, assistant professor of neurology at Yale University School of Medicine. "For some patients, the MRI looks bad, and they end up doing well. On the other hand, some have an MRI that looks good, and they don't do so well.''

But scientists are beginning to understand at least some of the molecular mechanisms involved in how and why the disease progresses -- including what triggers an immune system attack on myelin, the layered, fatty sheath that surrounds and protects the body's nerve cells.

Researchers at the University of Connecticut Health Center and Yale University Medical School have found that one antibody to a myelin protein could prove to be a valuable tool to diagnose the likely severity of a case of multiple sclerosis.

Myelin facilitates the transmission of the chemical and electrical signals that link the central nervous system, the brain and the rest of the body.

MS results from the immune system's damage to the myelin. The initial symptoms - blurred vision or muscle weakness - are mild for most patients. The symptoms typically recur and sometimes worsen. In severe cases, MS can be disabling and can result in paralysis.

Antibodies to two myelin proteins - MOG, or myelin oligodendrocyte glycoprotein, and MBP, or myelin basic protein - have been found in many MS patients and are implicated in the damage to the central nervous system.

There is some evidence that certain levels of each antibody in the blood might indicate whether a patient will experience either a quick recurrence or a more severe form of the disease.

However, other studies assessing the importance of the antibodies have been inconclusive. For instance, the antibodies have been found in some people who have no symptoms of MS. So the mere presence of MOG and MBP - the proteins that attract the destructive antibodies - is not useful for diagnostic purposes.

In a recent study, researchers at the UConn Health Center and Yale Medical School focused on the antibody to MOG.

Using laboratory mice bred to exhibit symptoms similar to those of MS, UConn researchers Cecilia B. Marta and Steven E. Pfeiffer and Yale researchers Nancy H. Ruddle, Rebecca A. Sweet and Alfred R. Oliver investigated a variety of mechanisms, including the location of the antibodies that attack myelin cells.

In their work, published online last month in the journal Proceedings of the National Academy of Science, the scientists found that only MOG situated on the surface of the myelin cells attracted the antibodies that caused damage to the myelin tissue. The antibodies did not recognize MOG proteins situated within the cell.

"This is the kind of [diagnostic test] that could contribute to better prediction of disease severity," Marta says. "Not all antibodies to MOG lead to pathology, and we need a quick and easy way to identify which ones do."

Yet such a diagnostic test, if developed, may only identify a subset of MS patients, the researchers acknowledged. MS is turning out to be a complex disease that probably is triggered in several different ways and involves different immune system responses that can vary from patient to patient, Ruddle says.

While there is no cure for MS, doctors do have several treatments available. However, some of the treatments have potentially dangerous side effects. Developing a way to help predict which patients are at highest risk of severe disease would be of great value in determining whether to treat a patient aggressively, doctors say.

Hoping to be able to predict the course of MS, researchers are also refining imaging technology and seeking genetic markers associated with the disease, says Susan Raimondo, community programs director for the Greater Connecticut Chapter of the National Multiple Sclerosis Society.

"We do have a long way to go, but things are getting better," Raimondo says, adding that there is much greater recognition of the importance of diagnosis and early treatment.

"Right now, if you meet criteria for MS, we start you on treatment." says Dr. Les Wolfson, chief of neurology at Hartford Hospital. "The reality is that we can now slow progression of the disease. Of course, knowing who will develop malignant disease would be a useful bit of information."