title: Towards translational therapies for multiple system atrophy.
abstract: Multiple system atrophy (MSA) is a fatal adult-onset neurodegenerative disorder of uncertain etiopathogenesis manifesting with autonomic failure, parkinsonism, and ataxia in any combination. The underlying neuropathology affects central autonomic, striatonigral and olivopontocerebellar pathways and it is associated with distinctive glial cytoplasmic inclusions (GCIs, Papp-Lantos bodies) that contain aggregates of α-synuclein. Current treatment options are very limited and mainly focused on symptomatic relief, whereas disease modifying options are lacking. Despite extensive testing, no neuroprotective drug treatment has been identified up to now; however, a neurorestorative approach utilizing autologous mesenchymal stem cells has shown remarkable beneficial effects in the cerebellar variant of MSA. Here, we review the progress made over the last decade in defining pathogenic targets in MSA and summarize insights gained from candidate disease-modifying interventions that have utilized a variety of well-established preclinical MSA models. We also discuss the current limitations that our field faces and suggest solutions for possible approaches in cause-directed therapies of MSA.
authors.affiliation: Department of Neurology, Innsbruck Medical University, Anichstraße 35, Innsbruck 6020, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kuzdas-Wood
authors.affiliation: Department of Neurology, Innsbruck Medical University, Anichstraße 35, Innsbruck 6020, Austria.
authors.forename: Nadia
authors.initials: N
authors.lastname: Stefanova
authors.affiliation: Institute of Clinical Neurobiology, Vienna, Austria.
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Jellinger
authors.affiliation: Department of Neurology, Innsbruck Medical University, Anichstraße 35, Innsbruck 6020, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Seppi
authors.affiliation: Divisions of Neuroscience and Neurology, The Ottawa Hospital Research Institute, University of Ottawa, 451 Smyth Road, RGH #1412, Ottawa, ON, K1H 8M5, Canada.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Schlossmacher
authors.affiliation: Department of Neurology, Innsbruck Medical University, Anichstraße 35, Innsbruck 6020, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Poewe
authors.affiliation: Department of Neurology, Innsbruck Medical University, Anichstraße 35, Innsbruck 6020, Austria. Electronic address: gregor.wenning@i-med.ac.at.
authors.forename: Gregor K
authors.initials: GK
authors.lastname: Wenning
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D006801:Humans; D008928:Mitochondria / Q000502:physiology; D019578:Multiple System Atrophy / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy*; D018384:Oxidative Stress / Q000502:physiology; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051844:alpha-Synuclein
keywords: Alpha-synuclein; Multiple system atrophy; Neurodegeneration; Olivopontocerebellar atrophy; Striatonigral degeneration