http://dailynews.yahoo.com/h/nm/20010803/hl/vaccine_1.html
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Friday
August 3 11:08 AM ET
By Will Dunham
WASHINGTON (Reuters) - A new vaccine blocked the development of Alzheimer's
disease (news
- web
sites) in mice genetically engineered to carry a human gene for the
degenerative brain disease, researchers said on Thursday.
Researchers at New York University School of Medicine said they expected to
test the vaccine in initial human clinical trials within a year. They also
expressed optimism that the vaccine would prove to be safer than another one
already being tested in human clinical trials.
``The potential for vaccination as a therapeutic approach for Alzheimer's
disease is something that's very exciting,'' Dr. Thomas Wisniewski, an author
of the study, said in an interview. ``But this (new vaccine) is a particularly
good line of investigation. And it looks like it will be translated very
rapidly to human use.''
Alzheimer's disease is characterized by the destruction of nerve cells,
especially in the areas of the brain responsible for memory and learning.
Abnormal structures in the brain called plaques are one of the hallmarks of the
disease. As the plaques accumulate, nerve cell connections are reduced. The
plaques are made up of deposits of a protein called amyloid beta, which is
toxic to cells and can damage and kill them.
Wisniewski and colleagues Dr. Blas Frangione and Einar Sigurdsson injected
the new vaccine into 11-month-old mice that had been genetically engineered
with a human gene for Alzheimer's disease. At that age, the mice already had
formed amyloid plaques in the brain. Seven months later, the researchers
examined the brains of the mice.
They found that the amount of amyloid plaque was reduced by 89% in the
cortex, the center of higher thought, and by 81% in the hippocampus, the memory
center, compared with the brains of mice that also had been genetically
engineered but were not given the vaccine. The vaccinated mice also had 57%
less of the protein that fosters the development of amyloid plaque.
The study appears in the American Journal of Pathology.
Four million Americans have Alzheimer's disease, including one in 10 of
people over age 65 and nearly half of those over 85, according to the
Alzheimer's Association. The group said that without a cure or prevention, the
number will jump to 14 million by 2050.
Alzheimer's is a progressive, degenerative brain disease whose victims
experience confusion, personality and behavior changes and impaired judgment.
Most people with Alzheimer's disease become unable to care for themselves.
The vaccine already in human clinical trials showed promise in mice less
than two years ago. That vaccine is made of a fragment of amyloid-precursor
protein.
Wisniewski expressed concern that the make-up of the first vaccine could be
toxic to nerve cells in the brain and by itself may lead to the development of
plaque.
In previous studies, the NYU team blocked the formation of amyloid plaque in
the brains of rats by creating a short peptide, a fragment of a protein. This
peptide prevented the formation of a toxic, insoluble form of amyloid that is
deposited in plaques in the brain.
The new vaccine is based on a modified, nontoxic peptide, the researchers
said.
``We believe that our peptide vaccine isn't toxic to nerve cells because it
doesn't aggregate into clumps; it remains in solution,'' Frangione said.
Wisniewski said he hoped the new vaccine could be ``a much more appropriate
choice for future human studies'' than the one already being tested. He said
the NYU team is looking for a corporate partner as the vaccine moves into human
trials.
``The hope here in particular is that this will work well because the effect
in the animal model is so dramatic, and also because the amyloid lesions that
you have in the animals are so similar to what you have in humans,'' Wisniewski
said.
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