A Sweet Solution for Alzheimer's Disease?
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ALZHEIMER'S DISEASE ST GEORGE-HYSLOP INOSITOL SCYLLO-INOSITOL AMYLOID
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Certain variants of a simple sugar ameliorate Alzheimer's-like disease
in mice, according to a new study by Canadian researchers. Although the
studies are still in the early stages, the findings could lead to new
therapies that prevent or delay the onset of Alzheimer's disease.



Newswise - Certain variants of a simple sugar ameliorate
Alzheimer's-like disease in mice, according to a new study by Canadian
researchers. Although the new studies are still in the early stages,
the findings could lead to new therapies that prevent or delay the
onset of Alzheimer's disease.

The new studies show that some types of a sugar called
cyclohexanehexol-also known as inositol-prevented the accumulation
of amyloid ? deposits, a hallmark of Alzheimer's disease.
Scyllo-inositol treatment also improved cognitive abilities in the mice
and allowed them to live a normal lifetime. The study appeared in
advance online publication of the journal Nature Medicine on June 11,
2006.

HHMI international research scholar and senior author Peter St
George-Hyslop cautioned that the chemicals tested in these studies are
not the type of inositol sold commercially as a nutritional supplement.
That type-myo-inositol-has been shown previously to be ineffective
at breaking up amyloid aggregates, he said.

In the brain of a person with Alzheimer's disease, small proteins
called amyloid ? aggregate into plaques, and a protein called tau
clumps into neurofibrillary tangles. The brain becomes inflamed and
neurons atrophy and die. It's not completely clear what kind of amyloid
? peptide (monomers, oligomeric aggregates, or fibrillar aggregates) is
responsible for the onset of disease, said St George-Hyslop of the
University of Toronto. "Because we were able to show that
scyllo-inositol specifically dispersed the high-molecular-weight
oligomeric aggregates, this study confirms that the initiating event is
the accumulation of oligomeric aggregates of amyloid ? peptide," he
said.

Previous work by JoAnne McLaurin, also of the University of Toronto and
lead author of the Nature Medicine paper, showed that several types of
inositol could stop amyloid proteins from aggregating in test tubes. To
see if these compounds could do the same in living animals, St
George-Hyslop, McLaurin, and colleagues tested them in transgenic mice
with human genes that predispose them to an Alzheimer's-like disease.

When the researchers treated these mice with scyllo-inositol, all of
the animals' disease symptoms improved. Cognitive function was
improved, amyloid plaques disappeared, inflammation declined, and the
mice lived longer.

The scientists found that scyllo-inositol conferred these benefits not
only if the mice were treated when they were very young and
disease-free, but also if they were treated after the onset of disease.

As a model system, these mice "are pretty good, but they're not a
perfect replica of the disease," St George-Hyslop said. The mice do
not develop tau tangles, he explained, but they are prone to amyloid
plaques, brain inflammation, cognitive disturbance, and early death,
just like humans with Alzheimer's disease.

The researchers found that the scyllo-inositol worked better than the
epi-inositol version. Scyllo-inositol produced more dramatic benefits
overall, while epi-inositol worked only transiently and only when given
before disease symptoms appeared.

Scyllo-inositol "is an exciting experimental therapy, but until it
has actually been tested in humans, it should not be considered the
cure for Alzheimer's disease," St George-Hyslop said. "There are
many things that are very promising when done in animal models that
turn out to either not work in humans or to have unexpected
toxicity."

A public Canadian company called Transition Therapeutics has regulatory
approval for clinical trials of scyllo-inositol in humans with
Alzheimer's disease and started them about a week ago. St George-Hyslop
has a small financial interest in the company.

St George-Hyslop and his colleagues are optimistic that scyllo-inositol
will be less toxic to humans than some previous drug candidates for
Alzheimer's disease. A vaccine designed to destroy amyloid ?, for
example, was first tested successfully in the same type of mice used in
the scyllo-inositol studies, but the vaccine turned out to be toxic in
some humans. It caused an autoimmune reaction in about 10 percent of
patients who were immunized, St George-Hyslop said.

Autoimmune responses shouldn't be a problem with scyllo-inositol.
"This compound works by a different mechanism and doesn't involve
immunizing a patient with his own protein, which was probably the
origin of the allergic reaction to the vaccine," the researcher said.

Another complication with previous attempts to treat Alzheimer's
disease has been that some compounds-such as beta secretase
inhibitors-cannot enter the brain easily, St George-Hyslop explained.
Scyllo-inositol, on the other hand, readily passes through the
blood-brain barrier where it is made available to the central nervous
system.

Even if scyllo-inositol does prove safe and effective in humans,
patients will likely still need drugs designed to attack other aspects
of Alzheimer's pathology, such as tau neurofibrillary tangles, St
George-Hyslop said.

"Alzheimer's disease is probably going to be treated by a cocktail of
drugs," he predicted. "Some of them might be this compound, or one
like it, that blocks the toxicity and aggregation of amyloid."


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