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Parkinson's disease, vaccine approach shows promise

A research has showed promising results in mice of a vaccine approach to treating Parkinson’s and similar diseases. These findings appear in the journal Neuron.

Eliezer Masliah, at the University of California, San Diego ( UCSD ), and colleagues 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 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.

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.”

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.

Source: University of California, San Diego, 2005