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Drug repurposing for disease-modifying effects in multiple system atrophy.

Seong Ho Jeong1,2, Jin Young Shin1,3, Phil Hyu Lee4,5

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Summary

Repurposed drugs show promise for Multiple System Atrophy (MSA), a progressive neurodegenerative disease. While many failed in trials, ubiquinol demonstrated disease modification, offering hope for future treatments.

Keywords:
Drug repurposingMultiple system atrophyNeurodegenerationα-Synuclein

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Drug Discovery

Background:

  • Multiple system atrophy (MSA) is a severe neurodegenerative disorder with no effective disease-modifying treatments.
  • Drug repurposing is a viable strategy to expedite the development of novel therapies for MSA.

Purpose of the Study:

  • To review repurposed drugs investigated for disease modification in MSA.
  • To analyze agents targeting key pathological pathways like alpha-synuclein aggregation, neuroinflammation, mitochondrial dysfunction, and impaired neurotrophic support.

Main Methods:

  • Systematic review of preclinical (in vitro, animal) studies and clinical trials of repurposed drugs for MSA.
  • Focus on drugs targeting specific MSA pathogenic mechanisms.

Main Results:

  • Numerous repurposed drugs showed preclinical promise but largely failed in clinical trials.
  • Ubiquinol is a notable exception, with a Phase 2 trial demonstrating significant motor progression reduction, marking the first placebo-controlled disease modification evidence in MSA.
  • Past trials faced limitations including small sample sizes, late patient enrollment, and tolerability issues.

Conclusions:

  • Despite past trial challenges, repurposed drugs, particularly ubiquinol, offer potential for MSA treatment.
  • Ongoing research, improved trial designs, and biomarker development are crucial for advancing disease-modifying therapies for MSA.