Recent Advances in Clinical Trials in Multiple System Atrophy
Curr Neurol Neurosci Rep. 2024-02-28; 24(4): 95-112
DOI: 10.1007/s11910-024-01335-0
Lire sur PubMed
Bendetowicz D(1)(2), Fabbri M(3)(4), Sirna F(5), Fernagut PO(6), Foubert-Samier
A(7)(8)(5), Saulnier T(5), Le Traon AP(3)(4), Proust-Lima C(5), Rascol O(3)(4),
Meissner WG(7)(8)(9).
Author information:
(1)Univ. Bordeaux, CNRS, IMN, UMR5293, Bordeaux, France.
.
(2)CHU Bordeaux, Service de Neurologie des Maladies Neurodégénératives, IMNc,
CRMR AMS, NS-Park/FCRIN Network, Bordeaux, France.
.
(3)MSA French Reference Center, Univ. Hospital Toulouse, Toulouse, France.
(4)Univ. Toulouse, CIC-1436, Departments of Clinical Pharmacology and
Neurosciences, NeuroToul COEN Center, NS-Park/FCRIN Network, Toulouse University
Hospital, Inserm, U1048/1214, Toulouse, France.
(5)Univ. Bordeaux, INSERM, BPH, U1219, IPSED, Bordeaux, France.
(6)Université de Poitiers, Laboratoire de Neurosciences Expérimentales et
Cliniques, INSERM UMR-S 1084, Poitiers, France.
(7)Univ. Bordeaux, CNRS, IMN, UMR5293, Bordeaux, France.
(8)CHU Bordeaux, Service de Neurologie des Maladies Neurodégénératives, IMNc,
CRMR AMS, NS-Park/FCRIN Network, Bordeaux, France.
(9)Department of Medicine, University of Otago, Christchurch, and New Zealand
Brain Research Institute, Christchurch, New Zealand.
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.
© 2024. The Author(s), under exclusive licence to Springer Science+Business
Media, LLC, part of Springer Nature.