Multiple system atrophy: a prototypical synucleinopathy for disease-modifying therapeutic strategies.
Neurobiology of Disease. 2014-07-01; 67: 133-139
DOI: 10.1016/j.nbd.2014.03.021
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1. Neurobiol Dis. 2014 Jul;67:133-9. doi: 10.1016/j.nbd.2014.03.021. Epub 2014 Apr
12.
Multiple system atrophy: a prototypical synucleinopathy for disease-modifying
therapeutic strategies.
Fernagut PO(1), Dehay B(1), Maillard A(2), Bezard E(3), Perez P(2), Pavy-Le Traon
A(4), Rascol O(5), Foubert-Samier A(6), Tison F(6), Meissner WG(7).
Author information:
(1)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France.
(2)CHU de Bordeaux, Unité de Soutien Méthodologique à la Recherche Clinique
(USMR), Pôle de santé publique, Bordeaux, France.
(3)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France; Service de Neurologie, CHU de Bordeaux, F-33604 Pessac,
France.
(4)Centre de référence atrophie multisystématisée, CHU de Toulouse, Toulouse,
France.
(5)Centre de référence atrophie multisystématisée, CHU de Toulouse, Toulouse,
France; Department of Clinical Pharmacology, University Hospital and University
of Toulouse 3, Toulouse, France; Department of Neurosciences, University Hospital
and University of Toulouse 3, Toulouse, France; INSERM UMR825 and CIC9302,
Toulouse, France.
(6)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France; Service de Neurologie, CHU de Bordeaux, F-33604 Pessac,
France; Centre de référence atrophie multisystématisée, CHU de Bordeaux, Pessac,
France.
(7)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France; Service de Neurologie, CHU de Bordeaux, F-33604 Pessac,
France; Centre de référence atrophie multisystématisée, CHU de Bordeaux, Pessac,
France. Electronic address: .
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.
Copyright © 2014 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.nbd.2014.03.021
PMID: 24727096 [Indexed for MEDLINE]