title: Multiple system atrophy: a prototypical synucleinopathy for disease-modifying therapeutic strategies.
abstract: Despite active fundamental, translational and clinical research, no therapeutic intervention has yet shown convincing effects on disease progression in Parkinson's disease (PD) patients. Indeed, several disease-modification trials failed or proved to be inconclusive due to lack of consistency between clinical rating scales and putative surrogate markers of disease progression, or confounding symptomatic effects of the tested compound. Multiple system atrophy (MSA) is a rapidly progressing orphan disorder leading to severe motor disability within a few years. Together with PD and dementia with Lewy bodies (DLB), MSA belongs to the synucleinopathies, a group of neurodegenerative disorders characterized by the abnormal accumulation of alpha-synuclein. Crucial milestones have been reached for successfully conducting clinical intervention trials in a large number of patients with MSA. In this personal view, we will review evidence, and discuss why MSA could prove the most relevant clinical model for assessing treatments that target mechanisms operating in all synucleinopathies.
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Fernagut
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Dehay
authors.affiliation: CHU de Bordeaux, Unité de Soutien Méthodologique à la Recherche Clinique (USMR), Pôle de santé publique, Bordeaux, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Maillard
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; Service de Neurologie, CHU de Bordeaux, F-33604 Pessac, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bezard
authors.affiliation: CHU de Bordeaux, Unité de Soutien Méthodologique à la Recherche Clinique (USMR), Pôle de santé publique, Bordeaux, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Perez
authors.affiliation: Centre de référence atrophie multisystématisée, CHU de Toulouse, Toulouse, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Pavy-Le Traon
authors.affiliation: Centre de référence atrophie multisystématisée, CHU de Toulouse, Toulouse, France; Department of Clinical Pharmacology, University Hospital and University of Toulouse 3, Toulouse, France; Department of Neurosciences, University Hospital and University of Toulouse 3, Toulouse, France; INSERM UMR825 and CIC9302, Toulouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Rascol
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; Service de Neurologie, CHU de Bordeaux, F-33604 Pessac, France; Centre de référence atrophie multisystématisée, CHU de Bordeaux, Pessac, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Foubert-Samier
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; Service de Neurologie, CHU de Bordeaux, F-33604 Pessac, France; Centre de référence atrophie multisystématisée, CHU de Bordeaux, Pessac, France.
authors.forename: François
authors.initials: F
authors.lastname: Tison
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; Service de Neurologie, CHU de Bordeaux, F-33604 Pessac, France; Centre de référence atrophie multisystématisée, CHU de Bordeaux, Pessac, France. Electronic address: wassilios.meissner@chu-bordeaux.fr.
authors.forename: Wassilios G
authors.initials: WG
authors.lastname: Meissner
mesh_terms: D001921:Brain / Q000378:metabolism; D002986:Clinical Trials as Topic; D006801:Humans; D019578:Multiple System Atrophy / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D010300:Parkinson Disease / Q000628:therapy; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein
keywords: Alpha-synuclein; Disease-modifying; Multiple system atrophy; Synucleinopathies; Therapeutic strategies