Specific Fats in Cerebrospinal Fluid of MS Patients May Be Telling Markers of Disease, Study Suggests

Testing for the types of fat (lipid) molecules present in the cerebrospinal fluid (CSF) of people with multiple sclerosis (MS) may be a very useful way to diagnose and monitor the disease, a study suggests.

“MS patients present a different lipid profile at the time of diagnosis” than do people without this disease, and that difference is “statistically significant,” researchers wrote in the study “Lipid profile of cerebrospinal fluid in multiple sclerosis patients: a potential tool for diagnosis,” which was published in the journal Scientific Reports.

In MS, a person’s immune system attacks myelin, the coating surrounding nerve fibers, damaging them. This damage slows or stops the transmission of nerve signals between the brain and spinal cord (the central nervous system, or CNS).

Myelin sheaths are made of protein and fatty substances and act as insulators, allowing electrical impulses to be transmitted quickly and efficiently along nerve cells.

While the root cause of MS remains unclear, but is believed to be a consequence of a combination of factors, some researchers have proposed that alterations in lipids may be important factors.

Lipids, fat-soluble constituents of living cells, play diverse roles in the CNS. Cholesterol, for instance, is important for the formation of junctions (synapses) used by nerve cells to communicate; fatty acids are precursors of signaling and structural lipids; and certain lipid species, like glycerophospholipids and glycosphingolipids, are involved i the formation of cell membranes, while corticoids and prostaglandins mediate inflammation.

Myelin is very rich in lipids, with 70% to 85% of its dry weight being composed of fats. It also contains about 700 different lipid species, particularly sphingolipids and glycerophospholipids. (Sphingolipids are important in signal transmission and cell recognition, and are believed to protect the cell surface from harmful environmental factors. With glycerophospholipids, sphingolipids also are suspected to have a role in MS and other demyelinating diseases, the researchers noted.)

Some studies suggest that lipid mediators are involved in autoimmune attacks against nerve cells. Antibodies targeting lipids are thought to be linked to a more aggressive MS disease course, and alterations in specific lipid groups have been detected in the brains of MS patients.

However, the specific changes in lipid composition that take place over the course of this disease, including at its onset, are still not clear.

Researchers at Universitat de Lleida and Hospital Universitario Arnau de Vilanova Hospital (HUAV), both in Spain, investigated this issue.

They compared the global set of lipids (lipidomics) found in 107 cerebrospinal fluid (CSF) samples taken from MS patients when diagnosed at their hospital from 2001 to 2005, with samples from people without MS (the control group). In total, samples from 53 relapse-remitting MS (RRMS) patients and 54 controls were studied.

CSF “is the body fluid that best reflects brain environment, thanks to its close contact with this organ and its nutritional and scavenger functions,”  researchers wrote. In this way, examining the CSF samples offered the scientists a window with which to explore early changes taking place in the CNS and myelin.

Data showed that the cerebral spinal fluid of MS patients differed in “statistically significant” ways from controls in 155 lipid species, 47 of which were identified: 30 glycerolipids, five sterol lipids, four fatty acids (FAs), five glycerophospholipids, and three sphingolipids.

Further analysis supported the existence of a “specific lipidomic signature” — that is, a specific pattern of lipid types and their levels that was able to discriminate (with a 70% accuracy) between MS patients at diagnosis and non-MS patients.

This signature was composed of 15 fat species belonging to five lipid families, including four glycerolipids, two sterol lipids (cholest-5-en-3alpha-ol and dihydrotestosterone), one fatty acid (tridecanoic acid), and one glycerophospholipid.

At least one MS therapy also appears to support a role for lipids in the disease.

“It is noteworthy that fingolimod [Gilenya, by Novartis], an effective treatment for MS, is an antagonist [blocker] of sphingosine-1-phosphate (sphingolipid). This highlights the importance of this lipid family, whose levels, according to our results, are altered in CSF following disease onset,” the researchers wrote.

With this global view obtained, the researchers then analyzed fatty acids in more detail, finding higher-than-usual levels in two members of this family: 18:3n3 (alfa linolenic acid) and 20:0 (arachidic acid). The latter is a saturated fatty acid, they said, and these types of fatty acids “are implicated in inflammation, a very relevant pathological process” and one likely to precede MS onset.

“MS causes changes in the lipidomic CSF profile that could be considered as a potential diagnostic tool … [that] would make therapeutic decisions easier improving patients’ quality of life,” the researchers concluded.

“[T]he description of the CSF lipidomic profile in the time of diagnosis could help to better understand the physiopathology of MS in early stages, to define the role of lipid metabolism in disease progression and to propose new biomarkers for monitoring the disease,” they wrote, noting “this information could be useful for new drugs development.”