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Current experimental disease-modifying therapeutics for multiple system atrophy.

Miguel Lemos1, Gregor K Wenning1, Nadia Stefanova2

  • 1Laboratory for Translational Neurodegeneration Research, Division of Neurobiology, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.

Journal of Neural Transmission (Vienna, Austria : 1996)
|August 16, 2021
PubMed
Summary

Multiple system atrophy (MSA) is a complex neurodegenerative disease lacking effective treatments. Research explores targeting alpha-Synuclein, neuroinflammation, and neuroprotection to modify MSA progression.

Keywords:
ImmunotherapyMultiple system atrophyNeuroinflammationSmall moleculesSynucleinTherapy

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Area of Science:

  • Neuroscience
  • Neurology
  • Pathology

Background:

  • Multiple system atrophy (MSA) is a rare, fatal neurodegenerative disorder.
  • Characterized by parkinsonism, ataxia, autonomic dysfunction, and rapid progression.
  • Definitive diagnosis requires post-mortem identification of glial cytoplasmic inclusions (GCIs) composed of aggregated alpha-Synuclein (α-Syn).

Purpose of the Study:

  • To review current disease-modifying treatment strategies for MSA.
  • To summarize therapeutic approaches based on MSA pathogenesis and recent research.
  • To highlight challenges in translating preclinical findings to clinical success.

Main Methods:

  • Review of preclinical and clinical therapeutic studies over the past two decades.
  • Analysis of approaches targeting α-Syn pathology, neuroinflammation, and neuroprotection.
  • Synthesis of current understanding of MSA pathogenesis.

Main Results:

  • α-Syn accumulation in oligodendrocytes is a key pathological event in MSA.
  • MSA is multifactorial, involving neuroinflammation, oxidative stress, and impaired neurotrophic support.
  • Several therapeutic strategies show promise but face translation challenges.

Conclusions:

  • Targeting α-Syn pathology, neuroinflammation, and neuroprotection are key disease-modifying strategies for MSA.
  • Overcoming the gap between preclinical and clinical studies is crucial for effective MSA treatment.
  • Further research is needed to develop successful disease-modifying therapies for MSA.