Stanford University, USA: azetidine-induced oligodendrogliopathy

Azetidine-induced oligodendrogliopathy

Principal Investigator: Raymond Sobel, M.D.
Institution: Stanford University
Country: USA
Amount Awarded: €75,000

In MS, myelin, the fatty substance that surrounds and protects nerve fibers, is destroyed. Myelin is made by cells in the brain called oligodendrocytes. This team proposes to investigate one way that oligodendrocytes may be rendered susceptible to MS early in life. They are focusing on the effects of a compound found in sugar beets called Azetidine-2-carboxylic acid (Aze). Sugar beets are used in meat and dairy products and their geographical use resembles that of MS incidence. Aze resembles an amino acid called proline. Amino acids are the building blocks of proteins, and if Aze is mistakenly incorporated into proteins instead of proline, the resulting protein may be unstable. Previous studies have shown that when Aze is incorporated into proteins made by oligodendrocytes, the cells do not function normally. The team will investigate the possibility that when fed to rodents early in life, Aze is a dietary contributor to susceptibility to MS pathology. If Aze is shown to be harmful to oligodendrocytes, the results will establish a new, highly relevant rodent model of MS and suggest new research to explore this possible clue to an MS trigger.

What does this mean for people living with progressive MS?

If susceptibility to MS is due at least in part to exposure to a dietary component early in life, this will suggest ways to prevent and perhaps treat MS.

Project Update

Status: Complete

Analysis of Aze-induced death of myelin producing cells shows that Aze induces nuclear swelling and cell death. The age-dependence of the cell death indicates greater vulnerability in early life, (i.e. the time of maximal myelin protein synthesis). High AZE doses resulted in clinical signs in mice and further analysis is underway. Results of long-term dosing with Aze are unclear at this time and need further study by the team.

Principal Investigator: Raymond Sobel

Raymond Sobel MDRaymond Sobel, MD, received a BS (Chemistry and Biology) from Stanford and medical degree from the University of California, San Francisco (UCSF). He trained in Pathology and Neuropathology at UCSF, University of California, Davis and Stanford University, and did a fellowship in Immunopathology at the Massachusetts General Hospital in Boston. Dr. Sobel has performed research on pathogenetic mechanisms in MS and EAE since 1981, and has authored or co-authored over 200 papers and book chapters on these subjects. He was President of the American Association of Neuropathologists in 2012 and is the Editor-in-Chief of the Journal of Neuropathology and Experimental Neurology. Current research projects address autoimmune mechanisms of reparative failure and oligodendrogliopathy, which lead to lesion and hence clinical progression in MS patients.

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