Multiple system atrophy: a prototypical synucleinopathy for disease-modifying therapeutic strategies

Neurobiol Dis. 2014 Jul:67:133-9. doi: 10.1016/j.nbd.2014.03.021. Epub 2014 Apr 12.


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.

Keywords: Alpha-synuclein; Disease-modifying; Multiple system atrophy; Synucleinopathies; Therapeutic strategies.

Publication types

  • Review

MeSH terms

  • Brain / metabolism
  • Clinical Trials as Topic
  • Humans
  • Multiple System Atrophy / metabolism
  • Multiple System Atrophy / pathology*
  • Multiple System Atrophy / therapy*
  • Parkinson Disease / therapy
  • alpha-Synuclein / metabolism*


  • alpha-Synuclein