Sugar supplement may treat immune disease
07 June 2007
NewScientist.com news service
Aria Pearson
http://www.newscientist.com/contents/issue/2607.html
"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 Michael 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).
"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 Thomas 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."
From issue 2607 of New Scientist magazine, 07 June 2007, page 20
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