An international team of investigators has found evidence suggesting that early in the course of MS, nerve cells, and not just their myelin insulation, show signs of damage by leaving traces of nerve cell proteins in the spinal fluid. The investigators, led by Steven Schutzer, MD, at Rutgers University New Jersey Medical School, sought to better understand which brain regions are initially targeted in MS. Understanding initial events in the development of MS may suggest ways to develop more effective therapies. The study, funded by the National Institutes of Health, was published on September 10, 2013 in the online free-access journal PLoS One
MS involves immune system attacks to the brain and spinal cord. Nerve fibers and nerve cells may also be damaged, leading to long-term deficits in people with MS. Understanding the sequence of events that lead to nervous system damage would offer insights into the cause of MS and new targets and tools for the development of better treatments.
The “white matter” in the brain consists of nerve fibers, which transmit messages to, from, and throughout the brain, and myelin. Myelin, the fatty substance that surrounds and protects nerve fibers, is white in color and is a major target of the immune system in MS. The “gray matter” in the brain includes the nerve cells and several associated structures. Recent research suggests that the gray matter is also a target of MS attacks, but it has not been clear how early in the disease this may occur.
Dr. Schutzer and his team looked at samples of spinal fluid, the liquid that surrounds the brain and spinal cord and that is obtained when someone undergoes a spinal tap. They compared spinal fluid from 6 healthy people, 12 people with definite relapsing-remitting MS, and 9 people with clinically isolated syndrome (CIS), which is a first neurological attack that often develops into MS. The people with CIS in this study later went on to develop definite MS, so their samples represent early MS, and the samples from people with relapsing MS represent later, well-established MS.
Dr. Schutzer and colleagues analyzed the proteins present in the spinal fluid samples and looked for differences among the three groups. The team found differences in protein content between samples from people with CIS and those with established relapsing MS. White matter proteins were similar between them, but those with CIS had evidence of gray matter proteins that may indicate debris from attacks to nerve cells. The researchers conclude that finding gray matter components in the spinal fluid of first-attack patients provides additional evidence for the idea that gray matter regions of the brain may be targeted early in the course of MS.
This study involved small numbers of patient samples, and as such its results are preliminary. Further studies will be needed to confirm these results, and to determine whether the immune system specifically targets gray matter components during the initial attack that eventually leads to MS.
The National MS Society is supporting studies aimed at understanding early events and pathology of MS, such as high-powered imaging studies exploring MS lesions in the gray matter, and studies to identify spinal fluid and blood markers that may serve as early indicators of disease activity. One example is a study by Dr. Gavin Giovannoni at University College London, testing the ability of a protein (neurofilament) in spinal fluid to serve as a signal that shows whether a therapy being tested for secondary-progressive MS can protect the nervous system from damage. If the spinal fluid test is a success, it would speed the search for treatments to stop MS progression.
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