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The source of this article is ScienceDaily: http://tinyurl.com/737nc

Source:   University Of California, San Diego

Date:   2005-06-29

A Vaccine Approach To Treating Parkinson's Disease
Researchers at the UCSD School of Medicine working with scientists at Elan
Pharmaceuticals, have reported promising results in mice of a vaccine
approach to treating Parkinson's and similar diseases. These results appear
in the June edition of the journal Neuron.

Dr. Eliezer Masliah, Professor of Neurosciences and Pathology at UCSD, and
colleagues at UCSD and Elan Pharmaceuticals in San Francisco, vaccinated
mice using a a combination of the protein that abnormally accumulates in
the brains of Parkinson's (called human alpha-synuclein) and an adjuvant.
This approach resulted in the generation of anti-alpha synuclein antibodies
in mice that are specially bred by Masliah's team to simulate Parkinson's
disease, resulting in reduced build-up of abnormal alpha-synuclein. The
accumulation of abnormal alpha-synuclein is associated with degeneration of
nerve cells and interference with normal inter-cellular communication,
leading to Parkinson's disease and dementia.

The work marks the first time a vaccine for this family of diseases has
been found effective in animal studies. Scientists at Elan Pharmaceuticals
have been working for the past few years in a vaccine for Alzheimer's Disease.

The researchers focused on a spectrum of neurological disorders called Lewy
body disease, which include Parkinson's and Alzheimer's. These disorders
are marked by the presence of Lewy bodies -- abnormal clumps of
alpha-synuclein -- in the brain. Normally, alpha-synuclein proteins support
communications between brain cells, or neurons. However, when abnormal
proteins clump together in the neurons, a build-up of synuclein can cut off
neuron activity, blocking normal signaling between brain cells and
ultimately choking the cells to death.

"We found that the antibodies produced by the vaccinated mice recognized
and reduced only the abnormal form of alpha-synuclein, since the protein's
normal form is in a cellular compartment where antibodies can't reach it,"
said Masliah. "Abnormal alpha-synuclein finds its way to the cell membrane,
where antibodies can recognize it."

Masliah stressed that the team's experimental active immunization, while
effective in mice, may not be as useful in humans. "We would not want to
actively immunize humans in this way by triggering antibody development,
because one could create harmful inflammation," he cautioned. "However, it
might be feasible to inject antibodies directly, as if the patient were
creating his or her own."

The team, the first to identify the presence of these proteins in the human
brain, originally thought the protein played an important role in the
development of Alzheimer's disease. Then, an explosion of research linked
Lewy bodies and their constituent proteins to both Alzheimer's and
Parkinson's. The team spent four years clarifying alpha-synuclein's role in
Parkinson's, developing a mouse model that contained the faulty and normal
genes for alpha-synuclein, and conducting the experiments that led to their
current findings.

With evidence that this approach could be effective in treating Lewy Body
disease, the UCSD researchers are now working with Elan Pharmaceuticals to
develop alternative ways to produce alpha-synuclein antibodies, with the
goal of making a vaccine that is safe and effective in humans. While this
research could take many years and holds no promise of prevention or cure,
the researchers are hopeful that the mouse studies are a step in the right
direction.

"This shows the first demonstration of a vaccine for this family of
disease," Masliah said.

Co-authors of the paper are Edward Rockenstein, Anthony Adame, Michael
Alford, Leslie Crews and Makoto Hashimoto, at UCSD, and Peter Seubert,
Michael Lee, Jason Goldstein, Tamie Chilcote, Dora Games, and Dale Schenk,
at Elan.

The research was supported by grants from Elan and the National Institute
of Aging.

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