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Review
. 2024 Apr;24(4):95-112.
doi: 10.1007/s11910-024-01335-0. Epub 2024 Feb 28.

Recent Advances in Clinical Trials in Multiple System Atrophy

David Bendetowicz  1   2 , Margherita Fabbri  3   4 , Federico Sirna  5 , Pierre-Olivier Fernagut  6 , Alexandra Foubert-Samier  7   8   5 , Tiphaine Saulnier  5 , Anne Pavy Le Traon  3   4 , Cécile Proust-Lima  5 , Olivier Rascol  3   4 , Wassilios G Meissner  7   8   9
Affiliations
Free article
Review

Recent Advances in Clinical Trials in Multiple System Atrophy

David Bendetowicz et al. Curr Neurol Neurosci Rep. 2024 Apr.
Free article

Abstract

Purpose of review: This review summarizes previous and ongoing neuroprotection trials in multiple system atrophy (MSA), a rare and fatal neurodegenerative disease characterized by parkinsonism, cerebellar, and autonomic dysfunction. It also describes the preclinical therapeutic pipeline and provides some considerations relevant to successfully conducting clinical trials in MSA, i.e., diagnosis, endpoints, and trial design.

Recent findings: Over 30 compounds have been tested in clinical trials in MSA. While this illustrates a strong treatment pipeline, only two have reached their primary endpoint. Ongoing clinical trials primarily focus on targeting α-synuclein, the neuropathological hallmark of MSA being α-synuclein-bearing glial cytoplasmic inclusions. The mostly negative trial outcomes highlight the importance of better understanding underlying disease mechanisms and improving preclinical models. Together with efforts to refine clinical measurement tools, innovative statistical methods, and developments in biomarker research, this will enhance the design of future neuroprotection trials in MSA and the likelihood of positive outcomes.

Keywords: Alpha-synuclein; Clinical trials; Disease-modifying therapies; Multiple system atrophy.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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