THURSDAY, April 24 (HealthDay News) -- German researchers are
reporting a new approach to the possible prevention of the
molecular "debris" that's associated with the development of
Alzheimer's disease.
The basic idea -- to block the activity of an enzyme called
beta-secretase -- is not new, said study lead author Dr. Kai
Simons, a professor of cell biology at the Max Planck Institute of
Molecular Cell Biology and Genetics in Dresden.
A number of laboratories, both academic and commercial, are
working on methods to prevent the enzyme from slicing a protein
into beta amyloid fragments that form the brain plaques found in
people with the disease. All work on the same principle. "If we
decrease the amount of cleavage, we could in all likelihood reduce
the likelihood of the disease," Simons said.
Most experts now agree that formation of the beta amyloid
plaques is directly linked to the development of Alzheimer's. The
problem with most proposed methods of blocking beta-secretase,
Simons said, is that they are designed to work outside of the
affected brain cells.
"This process of cleaving takes place inside cells," he said.
"We have constructed an inhibitor which binds outside, on the cell
membrane, and goes into the cell where the cleavage occurs."
Reporting in the April 25 issue of the journal
Science, Simons and his colleagues described both test-tube
experiments and animal studies in which the combination of an
anchoring molecule and a beta-secretase inhibitor reduced the
formation of beta amyloid plaque by more than 50 percent over four
hours, while the inhibitor alone was ineffective.
The success is just one small step toward a medically useful
preventive therapy for Alzheimer's disease, Simons acknowledged.
For one thing, the treatment was given by injection into the brains
of the experimental animals (fruit flies and mice), something not
likely to be done with people.
"This is proof of principle," Simons said. "The idea would be to
get it into the blood in humans and then over the blood-brain
barrier into the brain. There are many ways for molecules to get
into the brain."
The blood-brain barrier is a network of tightly packed cells
that prevents most molecules from entering the brain.
William J. Netzer, an Alzheimer's researcher at the Fisher
Center for Alzheimer's Disease Research Foundation at Rockefeller
University in New York City, called the new study "a profoundly
interesting line of research."
"It is not implausible that one might improve the effectiveness
of a drug by coaxing it to go into a region where the enzymes it
blocks exist," Netzer said.
But medical use of such a product can raise questions, he said.
"When you put an inhibitor into a living being, the chemical you
put in can be modified in the body. Where a compound goes into a
cell is a complicated issue when you put it into a human being," he
added.
Dr. James Galvin, associate professor of neurology and
psychiatry at Washington University in St. Louis, called the German
research "a novel idea."
If the concept works, it would solve a puzzle about how to best
target the enzyme, Galvin said. And it is a concept with broader
medical possibilities, he said.
"You can potentially inhibit other enzymes where cleavage occurs
within membranes," he said.
More information
Learn more about Alzheimer's disease from the
U.S. Library of Medicine.
