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

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

Keywords

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

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Clinical Neurology
  • Neurology

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    Krismer, F., Jellinger, K. A., Scholz, S. W., Seppi, K., Stefanova, N., Antonini, A., Poewe, W., & 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