Cell-surface Sugar Defects May Trigger Nerve Damage In Multiple Sclerosis Patients

Science Daily — Defects on cell-surface sugars may promote the short-term inflammation and long-term neurodegeneration that occurs in the central nervous system of multiple sclerosis patients, according to University of California, Irvine researchers.

The findings also suggest that a dietary supplement similar to glucosamine may be useful as an oral therapy to correct these defects and to treat both the short-term and the long-term symptoms of the disease. "The findings raise the possibility that these may both be treated by metabolic therapy," said Dr. Michael Demetriou, an assistant professor of neurology, and microbiology and molecular genetics. "This is particularly important, as therapies are not currently available to treat neurodegeneration in MS."

In tests on mice, Demetriou found that genetic deficiencies in a process called protein glycosylation led to a spontaneous disease very similar to MS, including paralysis associated with inflammatory damage to the protective myelin coating on nerve cells and degeneration of axons and neurons. Protein glycosylation refers to the addition of specific sugars to proteins; virtually all cell-surface and secreted proteins have complex sugars attached to them.

MS is a two-stage disease, with initial attacks of inflammatory demyelination, which damages myelin, followed approximately 10 years later by a slow, progressive neurdegenerative phase marked by loss of axons and nerve cells.

The irreversible damage to the central nervous system induced by neurodegeneration in MS leads to long term disability, including paralysis, incoordination, dementia and pain, and is not targeted by currently available therapies.

Demetriou's findings provide the first genetic model of MS in which both inflammatory demyelination and neurodegeneration arise from defects in a single biological pathway.

In previous studies, Demetriou found that the dietary supplement N-acetylglucosamine (GlcNAc), which is similar but more effective than the widely available glucosamine, corrected defects in protein glycosylation in cells and inhibited inflammatory demyelination in mice. The new study opens the possibility that metabolic therapy with GlcNAc may also prevent neurodegeneration. Studies in humans are required to assess the potential of this therapy in MS.

Study results appear on the online version of the Journal of Biological Chemistry.

Sung-Uk Lee, Ani Grigorian, I-Ju Chen, Guoyan Gao and Dr. Tahseen Mozaffar of UC Irvine and Judy Pawling and Colin McKerlie of the Samuel Lunenfeld Research Institute in Toronto participated in the study, which was supported by the National Multiple Sclerosis Society, the Juvenile Diabetes Research Foundation, the Wadsworth Foundation and the National Institutes of Health.

Note: This story has been adapted from material provided by University of California, Irvine.

Sugar supplement may harbour cure for immune diseases

From our ANI Correspondent

London, June 8: University of California, Irvine researchers have found that a sugar supplement may help treat the overactive immune cells that are responsible for autoimmune diseases, such as multiple sclerosis (MS) and type 1 diabetes, and stop them attacking the body's tissues.

Lead researcher Michael Demetriou says that their finding is based on a study of N-acetylglucosamine (GlcNAc)-a compound similar to glucosamine, a dietary supplement taken by people with osteoarthritis that is known to have some immunosuppressive effects.

Autoimmune diseases are triggered when receptors on the outside of immune cells called T-helper 1 (Th1) cells start binding "self" antigens rather than pieces of foreign invaders. Anything that decreases the amount of binding should suppress the autoimmune response.

The researchers found that naturally occurring GlcNAc molecules attach to T-cell receptors and these GlcNAc "branches" form a lattice on the cell surface that prevents the receptors from clustering near where the antigens are located. They say that less clustering means less antigen binding, and less activation of Th1 cells, reducing the autoimmune reaction.

During the study, Mice given oral GlcNAc supplements were seen to have twice as much GlcNAc branching on their T-cell receptors as untreated mice. It was also found that T-cells engineered to cause the mouse equivalent of MS failed to do so if they had been incubated in GlcNAc first.

A daily oral dose of GlcNAc also prevented type 1 diabetes in mice genetically engineered to develop the disease.

"T-cells engineered to cause the mouse equivalent of multiple sclerosis failed to do so if they had been incubated in GlcNAc. I'm astounded by their outcomes," the New Scientist quoted Nick Giannoukakis, a pathologist at the University of Pittsburgh School of Medicine in Pennsylvania, as saying.

The researchers, however, warn that still there is need for evidence that glucosamine can reverse symptoms in animals with autoimmune diseases, rather than just preventing them from occurring in the first place. They say that more research is needed to prove the safety of glucosamine and GlcNAc supplements in humans with autoimmune disease.


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