Genetic markers found for severe form of multiple sclerosis

Vandenbark Lab

October 23, 2017

Story by Erik Robinson, above photo by Nadir Balba

The OHSU School of Medicine's Paper of the Month for October 2017 is "MIF and D-DT are potential disease severity modifiers in male MS subjects" published in the Proceedings of the National Academy of Sciences.

This project was led by co-senior author Arthur Vandenbark, Ph.D., senior research career scientist, VA Portland Health Care System, and professor of neurology and molecular microbiology and immunology, OHSU School of Medicine, and researchers at Yale University.

The team uncovered two related cytokines and associated genetic markers that may explain why some people develop progressive multiple sclerosis, or MS. The study points the way toward developing the first-ever treatment to prevent progressive forms of the disease.

Dr. Gil BenedekResearchers identified a cytokine, called macrophage migration inhibitory factor, or MIF, along with its homolog protein D-dopachrome tautomerase, or D-DT, that are associated with progressive MS. Cytokines are a type of protein that are important in signaling between cells in the body. These particular cytokines can worsen the disease by increasing inflammation within the central nervous system. Researchers also identified two genetic markers that enhance expression of MIF, and D-DT, 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. Even better, researchers are already developing a medication to stop the disease in its tracks.

 "If you start a therapy before the disease has progressed very far, you may be able to slow it or stop it," said Dr. Vandenbark. "We now have a target for slowing or preventing the transition from relapsing-remitting to progressive MS, a stage of MS which is much more severe." Full OHSU news story.



MIF and D-DT are potential disease severity modifiers in male MS subjects. Benedek G, Meza-Romero R, Jordan K, Zhang Y, Nguyen H, Kent G, Li J, Siu E, Frazer J, Piecychna M, Du X, Sreih A, Leng L, Wiedrick J, Caillier SJ, Offner H, Oksenberg JR, Yadav V, Bourdette D, Bucala R, Vandenbark AA. Acad Sci U S A. 2017 Sep 18. pii: 201712288. doi: 10.1073/pnas.1712288114. [Epub ahead of print]

More Published Papers

Pictured top photo, from left to right: Ha Nguyen, Jack Wiedrick, Arthur Vandenbark, Hilary Seifert, Vijayshree Yadav, Gail Kent, Halina Offner. Bottom photo: Gil Benedek

About the OHSU School of Medicine Paper of the Month

The OHSU School of Medicine spotlights a recently published faculty research paper each month. The goals are to describe to the public the exceptional research happening at OHSU as well as inform our faculty of the innovative work underway across the school’s departments, institutes and disciplines. The monthly paper is selected by Associate Dean for Basic Research Mary Heinricher, Ph.D. Learn more