title: Multiple system atrophy as emerging template for accelerated drug discovery in α-synucleinopathies.
abstract: There is evidence that the α-synucleinopathies Parkinson's disease (PD) and the Parkinson variant of multiple system atrophy (MSA-P) overlap at multiple levels. Both disorders are characterized by deposition of abnormally phosphorylated fibrillar α-synuclein within the central nervous system suggesting shared pathophysiological mechanisms. Despite the considerable clinical overlap in the early disease stages, MSA-P, in contrast to PD, is fatal and rapidly progressive. Moreover recent clinical studies have shown that surrogate markers of disease progression can be quantified easily and may reliably depict the rapid course of MSA. We therefore posit that, MSA-P may be exploited as a filter barrier in the development of disease-modifying therapeutic strategies targeting common pathophysiological mechanisms of α-synucleinopathies. This approach might reduce the number of negative phase III clinical trials, and, in turn, shift the available resources to earlier development stages, thereby increasing the number of candidate compounds validated.
authors.affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: florian.krismer@i-med.ac.at.
authors.forename: Florian
authors.initials: F
authors.lastname: Krismer
authors.affiliation: Institute of Clinical Neurobiology, Vienna, Austria. Electronic address: kurt.jellinger@univie.ac.at.
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Jellinger
authors.affiliation: Department of Neurology, The Johns Hopkins Hospital, Baltimore, MD 21287, USA. Electronic address: sonja.w.scholz@googlemail.com.
authors.forename: Sonja W
authors.initials: SW
authors.lastname: Scholz
authors.affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: klaus.seppi@uki.at.
authors.forename: Klaus
authors.initials: K
authors.lastname: Seppi
authors.affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: nadia.stefanova@i-med.ac.at.
authors.forename: Nadia
authors.initials: N
authors.lastname: Stefanova
authors.affiliation: Department of Parkinson's Disease and Movement Disorders, IRCCS San Camillo, Venice, Italy. Electronic address: angelo3000@yahoo.com.
authors.forename: Angelo
authors.initials: A
authors.lastname: Antonini
authors.affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: werner.poewe@i-med.ac.at.
authors.forename: Werner
authors.initials: W
authors.lastname: Poewe
authors.affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: Gregor.Wenning@i-med.ac.at.
authors.forename: Gregor K
authors.initials: GK
authors.lastname: Wenning
mesh_terms: D055808:Drug Discovery; D006801:Humans; D019578:Multiple System Atrophy / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D051844:alpha-Synuclein
keywords: Drug development; Multiple system atrophy; Parkinson's disease; Synucleinopathies