Brain’s gray matter may be first target of MS

Analysis of cerebrospinal fluid from patients recently diagnosed with multiple sclerosis provides the first solid physical evidence that the brain's gray matter plays a role in the disease. (Credit: Veer)

Multiple sclerosis may originate in a different part of the brain than previously believed, a finding that could explain why progress toward discovering the cause has been so elusive.

Until recently, most research on MS, a disease that affects up to half a million people in the United States, has focused on the brain’s white matter, which contains the nerve fibers.

And for good reason: symptoms of the disease, which include muscle weakness and vision loss, occur when there is deterioration of a fatty substance called myelin. The substance coats nerves contained in the white matter and acts as insulation for them.


When myelin in the brain is degraded, apparently by the body’s own immune system, and the nerve fiber is exposed, transmission of nerve impulses can be slowed or interrupted. So when patients’ symptoms flare up, the white matter is where the action in the brain appears to be.

But new research published in the journal PLOS ONE, suggests scientists should look more to the gray matter and less to the white. That approach could give physicians effective tools to treat MS far earlier than ever before.

Steven Schutzer, a a physician and scientist at Rutgers, attacked the problem from a new direction. He analyzed patients’ cerebrospinal fluid (CSF) by taking full advantage of a combination of technologies called proteomics and high-resolution mass spectrometry.

“Proteins present in the clear liquid that bathes the central nervous system can be a window to physical changes that accompany neurological disease,” he says, “and the latest mass spectrometry techniques allow us to see them as never before.”

In this study, he used that novel approach to compare the cerebrospinal fluid of newly diagnosed MS patients with that of longer term patients, as well as fluid taken from people with no signs of neurological disease.

What Schutzer found startled one of his co-investigators, Patricia K. Coyle of Stony Brook University. The proteins in the CSF of the new MS patients suggested physiological disruptions not only in the white matter of the brain where the myelin damage eventually shows up.

They also pointed to substantial disruptions in the gray matter, a different part of the brain that contains the axons and dendrites and synapses that transfer signals between nerves.

Several scientists have in fact hypothesized that there might be gray matter involvement in early MS, but the technology needed to test their theories did not yet exist.

The critical initial target

Schutzer’s analysis, which Coyle calls “exquisitely sensitive,” provides the solid physical evidence for the very first time.

It includes a finding that nine specific proteins associated with gray matter are far more abundant in patients who had just suffered their first attack than in longer term MS patients or in the healthy controls.

“This evidence indicates gray matter may be the critical initial target in MS rather than white matter,” says Coyle. “We may have been looking in the wrong area.”

That realization presents exciting possibilities, Coyle says. One is that patients who suffer attacks that appear related to MS could have their cerebrospinal fluid tested quickly. If proteins that point to early MS are found, helpful therapy could begin at once, before the disease can progress further.

The findings may also lead one day to more effective treatments for MS with far fewer side effects. Without specific knowledge of what causes multiple sclerosis, patients now need to take medications that can broadly weaken their immune systems.

These drugs slow the body’s destruction of myelin in the brain, but also degrade the immune system’s ability to keep the body healthy in other ways. The new research may set the stage for more targeted treatments that attack MS while preserving other important immune functions.

Schutzer sees an even broader future for the work he is now doing. He also has used advanced analysis of cerebrospinal fluid to identify physical markers for neurological ailments that include Lyme disease and chronic fatigue syndrome.

“When techniques are refined, more medical conditions are examined, and costs per patient come down, one day there could be a broad panel of tests through which patients and their doctors can get early evidence of a variety of disorders, and use that knowledge to treat them both more quickly and far more effectively than is possible now. ”

This National Institutes of Health funded the study.

Source: Rutgers