Sugar supplement may treat immune disease

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Sugar supplement may treat immune disease

07 June 2007

NewScientist.com news service

Aria Pearson

A sugar supplement may sweeten the overactive immune cells

responsible for autoimmune diseases such as multiple sclerosis (MS)

and type 1 diabetes and stop them attacking the body's tissues.

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.

Previous studies suggested that glucosamine, a dietary supplement

commonly taken by people with osteoarthritis, has some

immunosuppressive effects. This led Demetriou and colleagues

at the University of California, Irvine, to investigate a similar but

more potent compound called N-acetylglucosamine (GlcNAc).

A large number of proteins in the body are modified by the attachment

of sugar molecules to their surface through a process called

glycosylation, and altered glycosylation has been implicated in some

autoimmune diseases. Demetriou's team 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

(see Diagram). Less clustering means less antigen binding, and less

activation of Th1 cells, reducing the autoimmune reaction.

Mice given oral GlcNAc supplements had twice as much GlcNAc branching

on their T-cell receptors as untreated mice. The researchers 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 (The Journal of

Biological Chemistry, DOI: 10.1074/jbc.M701890200).

" 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, " says Nick Giannoukakis, a pathologist

at the University of Pittsburgh School of Medicine in Pennsylvania.

In 2002, he showed that glucosamine worked as well as standard

immunosuppressants in increasing the amount of time transplanted

hearts lasted in mice.

However, he warns that evidence is still needed that glucosamine or

GlcNAc can reverse symptoms in animals with autoimmune diseases,

rather than just preventing them from occurring in the first place.

There is some preliminary evidence to support this. In 2005,

Abdolmohamad Rostami's team at Jefferson University in

Philadelphia, Pennsylvania, showed that glucosamine can suppress MS

symptoms in mice that had recently developed the disease. Meanwhile,

a small study of 12 children with autoimmune inflammatory bowel

disease, suggested that GlcNAc lessened symptoms in eight of them.

Rostami also cautions that, as they are immunosuppressive, more

research is needed to prove the safety of glucosamine and GlcNAc

supplements in humans with autoimmune disease. Also, the blood-brain

barrier is open in MS patients and little is known about what these

compounds do in the brain, he says.