Study finds low sugar metabolite associates with disability, neurodegeneration in MS

Irvine, CA – May 13, 2021 – A new University of California, Irvine-led study finds low serum levels of the sugar N-acetylglucosamine (GlcNAc), is associated with progressive disability and neurodegeneration in multiple sclerosis (MS).

The study, done in collaboration with researchers from Charité – Universitätsmedizin Berlin, Germany, and the University of Toronto, Canada, is titled, “Association of a Marker of N-Acetylglucosamine With Progressive Multiple Sclerosis and Neurodegeneration,” The study was published this week in JAMA Neurology.

The study suggests that GlcNAc, which has been previously shown to promote re-myelination and suppress neurodegeneration in animal models of MS, is reduced in serum of progressive MS patients and those with worse clinical disability and neurodegeneration.

“We found the serum levels of a marker of GlcNAc was markedly reduced in progressive MS patients compared to healthy controls and patients with relapsing-remitting multiple sclerosis” explained Michael Demetriou, MD, PhD, FRCP(C), professor of neurology, microbiology and molecular genetics at UCI School of Medicine, and senior author on the paper.

First author of the study, Alexander Brandt, MD, adjunct associate professor of neurology at the UCI School of Medicine and previously associated with the Experimental and Clinical Research Center, Charité – Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Germany, added, “Lower GlcNAc serum marker levels correlated with multiple measures of neurodegeneration in MS, namely worse expanded disability status scale scores, lower thalamic volume, and thinner retinal nerve fiber layer. Also, low baseline serum levels correlated with a greater percentage of brain volume loss at 18 months,” he said.

GlcNAc regulates protein glycosylation, a fundamental process that decorates the surface of all cells with complex sugars. Previous preclinical, human genetic and ex vivo human mechanistic studies revealed that GlcNAc reduces proinflammatory immune responses, promotes myelin repair, and decreases neurodegeneration. Combined with the new findings, the data suggest that GlcNAc deficiency may promote progressive disease and neurodegeneration in patients with MS. However, additional human clinical studies are required to confirm this hypothesis.

“Our findings open new potential avenues to identify patients at risk of disease progression and neurodegeneration, so clinicians can develop and adjust therapies accordingly,” said Michael Sy, MD, PhD, assistant professor in residence in the Department of Neurology at UCI and a co-author of the study.

MS is characterized by recurrent episodes of neurologic dysfunction resulting from acute inflammatory demyelination. Progressive MS is distinguished by continuous inflammation, failure to remyelinate, and progressive neurodegeneration, causing accrual of irreversible neurologic disability. Neurodegeneration is the major contributor to progressive neurological disability in MS patients, yet mechanisms are poorly understood and there are no current treatments for neurodegeneration.

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This study was funded in part by a grant from the National Institute of Allergy and Infectious Disease and the National Center for Complimentary and Integrative Health as well as the Excellence Initiative and the Excellence Strategy of the German Federal and State Governments.

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