title: Active immunization against alpha-synuclein ameliorates the degenerative pathology and prevents demyelination in a model of multiple system atrophy.
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.
authors.affiliation: AFFiRiS AG, Vienna Biocenter, A-1030, Vienna, Austria. markus.mandler@affiris.com.
authors.forename: Markus
authors.initials: M
authors.lastname: Mandler
authors.affiliation: Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. evaleramartin@ucsd.edu.
authors.forename: Elvira
authors.initials: E
authors.lastname: Valera
authors.affiliation: Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. erockenstein@ucsd.edu.
authors.forename: Edward
authors.initials: E
authors.lastname: Rockenstein
authors.affiliation: Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. mmante@ucsd.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Mante
authors.affiliation: AFFiRiS AG, Vienna Biocenter, A-1030, Vienna, Austria. harald.weninger@affiris.com.
authors.forename: Harald
authors.initials: H
authors.lastname: Weninger
authors.affiliation: Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. cpatrick@ucsd.edu.
authors.forename: Christina
authors.initials: C
authors.lastname: Patrick
authors.affiliation: Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. asadame@ucsd.edu.
authors.forename: Anthony
authors.initials: A
authors.lastname: Adame
authors.affiliation: AFFiRiS AG, Vienna Biocenter, A-1030, Vienna, Austria. sabine.schmidhuber@affiris.com.
authors.forename: Sabine
authors.initials: S
authors.lastname: Schmidhuber
authors.affiliation: AFFiRiS AG, Vienna Biocenter, A-1030, Vienna, Austria. radmila.santic@affiris.com.
authors.forename: Radmila
authors.initials: R
authors.lastname: Santic
authors.affiliation: AFFiRiS AG, Vienna Biocenter, A-1030, Vienna, Austria. achim.schneeberger@affiris.com.
authors.forename: Achim
authors.initials: A
authors.lastname: Schneeberger
authors.affiliation: AFFiRiS AG, Vienna Biocenter, A-1030, Vienna, Austria. walter.schmidt@affiris.com.
authors.forename: Walter
authors.initials: W
authors.lastname: Schmidt
authors.affiliation: AFFiRiS AG, Vienna Biocenter, A-1030, Vienna, Austria. frank.mattner@affiris.com.
authors.forename: Frank
authors.initials: F
authors.lastname: Mattner
authors.affiliation: Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. emasliah@ucsd.edu.|Department of Pathology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. emasliah@ucsd.edu.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D003711:Demyelinating Diseases / Q000276:immunology / Q000517:prevention & control*; D004195:Disease Models, Animal; D008822:Mice, Transgenic; D017628:Microglia / Q000166:cytology / Q000276:immunology; D019578:Multiple System Atrophy / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D009474:Neurons / Q000166:cytology / Q000276:immunology; D009836:Oligodendroglia / Q000166:cytology / Q000276:immunology; D020734:Parkinsonian Disorders / Q000276:immunology / Q000473:pathology*; D014611:Vaccination / Q000379:methods; D051844:alpha-Synuclein / Q000276:immunology*
chemical_list: D051844:alpha-Synuclein