Turning Research Focus to Gray Matter Sheds Light on Multiple Sclerosis Origin

Though previous imaging studies have proposed that white matter dysfunction predicts the development of multiple sclerosis (MS), a recent study supported by the National Institutes of Health (NIH) suggests that those researchers were concentrating on the wrong area of the brain.

For their study on the involvement of gray matter in an initial MS attack, Steven E. Schutzer, MD, from the Rutgers New Jersey Medical School in Newark, NJ, and clinical investigators from Stony Brook University in Stony Brook, NY; Uppsala University in Sweden; the University of Szeged in Hungary; and the Pacific Northwest National Laboratory in Richland, WA, compared proteins in the cerebrospinal fluid (CSF) of newly-diagnosed MS patients (n= 9) to those in established relapsing-remitting MS (RRMS) patients (n=12) and healthy control subjects (n= 6) — given that CSF is “an important body fluid to examine in MS because recent evidence suggests cell processing within the central nervous system (CNS) is a crucial component to the damage process … (and) CSF is known to reflect the CNS microenvironment,” the authors wrote.

Using proteomic analysis and high-resolution mass spectrometry on the CSF samples from those three subject groups, the researchers detected 20 CNS-specific proteins that were significantly increased or decreased in the CSF of first-attack MS patients compared to RRMS patients and control subjects. According to the researchers, at least 15 of those proteins disrupt areas associated with gray matter — such as synapse, axon, and neuron functioning — as opposed to myelin components of nerve fibers associated with white matter. Those findings suggest that “gray matter rather than myelin is more proximally involved in the initiation of MS,” the authors wrote.

In a press release about the study, co-author Patricia K. Coyle, MD, director of the MS Comprehensive Care Center at Stony Brook University, said the “evidence that gray matter may be the critical initial target in MS rather than white matter” means that “patients who suffer attacks that appear related to MS could have their CSF tested quickly, (and) if proteins that point to early MS are found, helpful therapy could begin at once, before the disease can progress further.”

Coyle said that realization “may also one day lead to more effective treatments for MS with far fewer side effects,” since the current medications taken by MS patients slow the destruction of myelin but also weaken other important immune functions.