NAG Inhibits T Cell Activity & Treats Experimental Autoimmune Encephalomyelitis

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http://www.ncbi.nlm.nih.gov/pubmed/21965673

Current treatments and emerging oral therapies for multiple sclerosis (MS) are limited by effectiveness, cost, and/or toxicity. Genetic and environmental factors that alter the branching of Asn (N)-linked glycans result in T cell hyperactivity, promote spontaneous inflammatory demyelination and neurodegeneration in mice, and converge to regulate the risk of MS. The sugar N-acetylglucosamine (GlcNAc) enhances N-glycan branching and inhibits T cell activity and adoptive transfer experimental autoimmune encephalomyelitis (EAE). Here, we report that oral GlcNAc inhibits T-helper 1 (Th1) and T-helper 17 (Th17) responses and attenuates the clinical severity of myelin oligodendrocyte glycoprotein (MOG)-induced EAE when administered after disease onset.

 

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A LEF article concerning the study,

http://www.lef.org/whatshot/2011_10.htm#N-acetylglucosamine-may-help-combat-MS

October 3, 2011.In an article published online on September 29, 2011, inThe Journal of Biological Chemistry, researchers at the University of California, Irvine report that N-acetylglucosamine, a form of glucosamine (commonly used for arthritis), could be helpful in the treatment ofmultiple sclerosis, an autoimmune disease that affects an estimated 2.5 million men and women worldwide.

In their introduction to the article, Dr Michael Demetriou and colleagues remark that “Current treatments and emerging oral therapies for multiple sclerosis (MS) are limited by effectiveness, cost and/or toxicity.” In previous research, the team found that inherited and environmental risk factors converge to influence the manner in which specific sugars are added to proteins that regulate the disease.

The current study utilized a mouse model of MS-like autoimmune disease. Dr Demetriou’s team found that orally administered N-acetylglucosamine suppressed T-cell hyperactivity and autoimmune response when given after the onset of the disease via greater sugar modifications to T cell proteins. “This sugar-based supplement corrects a genetic defect that induces cells to attack the body in MS making metabolic therapy a rational approach that differs significantly from currently available treatments,” explained Dr Demetriou, who is an associate professor of neurology and microbiology & molecular genetics at UC Irvine.

An earlier study conducted by Dr Demetriou found that supplementation with N-acetylglucosamine was associated with a reduction in the growth and function of T-cells responsible for autoimmune attack in a mouse model of diabetes. Other research found improvements in autoimmune inflammatory bowel disease after two years of treatment with the compound. “Together, these findings identify metabolic therapy using dietary supplements such as N-acetylglucosamine as a possible treatment for autoimmune diseases,” Dr Demetriou stated. “Excitement about this strategy stems from the novel mechanism for affecting T-cell function and autoimmunity — the targeting of a molecular defect promoting disease — and its availability and simplicity.”