Multiple system atrophy as emerging template for accelerated drug discovery in α-synucleinopathies

Florian Krismer, Kurt A. Jellinger, Sonja W. Scholz, Klaus Seppi, Nadia Stefanova, Angelo Antonini, Werner Poewe, Gregor K. Wenning

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)793-799
Number of pages7
JournalParkinsonism and Related Disorders
Volume20
Issue number8
DOIs
Publication statusPublished - 2014

Fingerprint

Multiple System Atrophy
Drug Discovery
Parkinson Disease
Synucleins
Phase III Clinical Trials
Disease Progression
Central Nervous System
Biomarkers
Therapeutics

Keywords

  • Drug development
  • Multiple system atrophy
  • Parkinson's disease
  • Synucleinopathies

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Clinical Neurology
  • Neurology

Cite this

Krismer, F., Jellinger, K. A., Scholz, S. W., Seppi, K., Stefanova, N., Antonini, A., ... Wenning, G. K. (2014). Multiple system atrophy as emerging template for accelerated drug discovery in α-synucleinopathies. Parkinsonism and Related Disorders, 20(8), 793-799. https://doi.org/10.1016/j.parkreldis.2014.05.005

Multiple system atrophy as emerging template for accelerated drug discovery in α-synucleinopathies. / Krismer, Florian; Jellinger, Kurt A.; Scholz, Sonja W.; Seppi, Klaus; Stefanova, Nadia; Antonini, Angelo; Poewe, Werner; Wenning, Gregor K.

In: Parkinsonism and Related Disorders, Vol. 20, No. 8, 2014, p. 793-799.

Research output: Contribution to journalArticle

Krismer, F, Jellinger, KA, Scholz, SW, Seppi, K, Stefanova, N, Antonini, A, Poewe, W & Wenning, GK 2014, 'Multiple system atrophy as emerging template for accelerated drug discovery in α-synucleinopathies', Parkinsonism and Related Disorders, vol. 20, no. 8, pp. 793-799. https://doi.org/10.1016/j.parkreldis.2014.05.005
Krismer, Florian ; Jellinger, Kurt A. ; Scholz, Sonja W. ; Seppi, Klaus ; Stefanova, Nadia ; Antonini, Angelo ; Poewe, Werner ; Wenning, Gregor K. / Multiple system atrophy as emerging template for accelerated drug discovery in α-synucleinopathies. In: Parkinsonism and Related Disorders. 2014 ; Vol. 20, No. 8. pp. 793-799.
@article{a7728066d2ed43038d207232b3dd161a,
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.",
keywords = "Drug development, Multiple system atrophy, Parkinson's disease, Synucleinopathies",
author = "Florian Krismer and Jellinger, {Kurt A.} and Scholz, {Sonja W.} and Klaus Seppi and Nadia Stefanova and Angelo Antonini and Werner Poewe and Wenning, {Gregor K.}",
year = "2014",
doi = "10.1016/j.parkreldis.2014.05.005",
language = "English",
volume = "20",
pages = "793--799",
journal = "Parkinsonism and Related Disorders",
issn = "1353-8020",
publisher = "Elsevier BV",
number = "8",

}

TY - JOUR

T1 - Multiple system atrophy as emerging template for accelerated drug discovery in α-synucleinopathies

AU - Krismer, Florian

AU - Jellinger, Kurt A.

AU - Scholz, Sonja W.

AU - Seppi, Klaus

AU - Stefanova, Nadia

AU - Antonini, Angelo

AU - Poewe, Werner

AU - Wenning, Gregor K.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Drug development

KW - Multiple system atrophy

KW - Parkinson's disease

KW - Synucleinopathies

UR - http://www.scopus.com/inward/record.url?scp=84905241925&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84905241925&partnerID=8YFLogxK

U2 - 10.1016/j.parkreldis.2014.05.005

DO - 10.1016/j.parkreldis.2014.05.005

M3 - Article

VL - 20

SP - 793

EP - 799

JO - Parkinsonism and Related Disorders

JF - Parkinsonism and Related Disorders

SN - 1353-8020

IS - 8

ER -