New Markers Revealed for Severe Multiple Sclerosis

In MS, the sheath covering nerve fibers in the brain and spinal cord becomes damaged, slowing or blocking electrical signals from the brain reaching the eyes, muscles, and other parts of the body.

Two closely related cytokines, molecules involved in cell communication and movement, have been discovered that may explain why some people develop progressive multiple sclerosis (MS), the most severe form of the disease and this may help in developing a novel treatment to prevent progressive forms of the disease.

A large group of scientists working with those at VA Portland Health Care System (Portland, OR, USA) recruited 117 participants all over the age of 18. One hundred seventy plasma and 474 DNA samples of MS subjects were also received. Participants included subjects with clinically definite or laboratory-supported MS diagnosis according as well as subjects with clinically isolated syndrome (CIS) and 49 health controls (HC) were also enrolled Over 90% of the study participants were of European ancestry.

Plasma macrophage migration inhibitory factor (MIF) concentration was measured by the human MIF Quantikine enzyme-linked immunosorbent assay (ELISA) kit and its related protein, D-dopachrome tautomerase (D-DT) was also measured by an ELISA. The investigators performed real-time polymerase chains reactions (RT-PCR), histology, genotyping, cell surface CD74 measurements, which were analyzed on an Accuri C6 flow cytometer. The scientists used several other technologies to obtain their results.

The team identified the cytokine, MIF, along with its related protein, D-DT, which are associated with progressive MS. These cytokines worsen the disease by increasing inflammation within the central nervous system. They also linked enhanced expression of MIF with a gene variant that occurred more frequently in MS patients with progressive disease particularly in men.

These findings suggest that a simple genetic test could be used to identify MS patients at risk of developing the more severe form of the disease. As medications to halt the disease are under development, the scientists say that such a therapy could be used as part of a precision medicine approach that would be most effective in patients who have the MIF genetic susceptibility.

Richard Bucala, MD, a professor of medicine and co-senior author of the study, said, “The value of this discovery to patients is that there are now approved therapies, as well as new ones in development in the Oregon and Yale labs, which target the MIF pathway and could be directed toward progressive MS. Using a simple genetic test to select patients who might benefit the most from MIF blockers would accelerate drug development by reducing cost, decreasing risks of toxic effects, and providing a genetically tailored, effective treatment.” The study was published on September 18, 2017, in the journal Proceedings of the National Academy of Sciences.

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VA Portland Health Care System