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Mol Neurodegener. 2015 Mar 19;10:10. doi: 10.1186/s13024-015-0008-9.

Active immunization against alpha-synuclein ameliorates the degenerative pathology and prevents demyelination in a model of multiple system atrophy.

Author information

1
AFFiRiS AG, Vienna Biocenter, A-1030, Vienna, Austria. markus.mandler@affiris.com.
2
Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. evaleramartin@ucsd.edu.
3
Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. erockenstein@ucsd.edu.
4
Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. mmante@ucsd.edu.
5
AFFiRiS AG, Vienna Biocenter, A-1030, Vienna, Austria. harald.weninger@affiris.com.
6
Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. cpatrick@ucsd.edu.
7
Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. asadame@ucsd.edu.
8
AFFiRiS AG, Vienna Biocenter, A-1030, Vienna, Austria. sabine.schmidhuber@affiris.com.
9
AFFiRiS AG, Vienna Biocenter, A-1030, Vienna, Austria. radmila.santic@affiris.com.
10
AFFiRiS AG, Vienna Biocenter, A-1030, Vienna, Austria. achim.schneeberger@affiris.com.
11
AFFiRiS AG, Vienna Biocenter, A-1030, Vienna, Austria. walter.schmidt@affiris.com.
12
AFFiRiS AG, Vienna Biocenter, A-1030, Vienna, Austria. frank.mattner@affiris.com.
13
Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. emasliah@ucsd.edu.
14
Department of Pathology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. emasliah@ucsd.edu.

Abstract

BACKGROUND:

Multiple system atrophy (MSA) is a neurodegenerative disease characterized by parkinsonism, ataxia and dysautonomia. Histopathologically, the hallmark of MSA is the abnormal accumulation of alpha-synuclein (α-syn) within oligodendroglial cells, leading to neuroinflammation, demyelination and neuronal death. Currently, there is no disease-modifying treatment for MSA. In this sense, we have previously shown that next-generation active vaccination technology with short peptides, AFFITOPEs®, was effective in two transgenic models of synucleinopathies at reducing behavioral deficits, α-syn accumulation and inflammation.

RESULTS:

In this manuscript, we used the most effective AFFITOPE® (AFF 1) for immunizing MBP-α-syn transgenic mice, a model of MSA that expresses α-syn in oligodendrocytes. Vaccination with AFF 1 resulted in the production of specific anti-α-syn antibodies that crossed into the central nervous system and recognized α-syn aggregates within glial cells. Active vaccination with AFF 1 resulted in decreased accumulation of α-syn, reduced demyelination in neocortex, striatum and corpus callosum, and reduced neurodegeneration. Clearance of α-syn involved activation of microglia and reduced spreading of α-syn to astroglial cells.

CONCLUSIONS:

This study further validates the efficacy of vaccination with AFFITOPEs® for ameliorating the neurodegenerative pathology in synucleinopathies.

PMID:
25886309
PMCID:
PMC4411775
DOI:
10.1186/s13024-015-0008-9
[Indexed for MEDLINE]
Free PMC Article

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