Journal Article

DZNE-2024-00502

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson's disease.

Pagano, G. ; Taylor, K. I. ; Anzures Cabrera, J. ; Simuni, T. ; Marek, K. ; Postuma, R. B. ; Pavese, N. ; Stocchi, F. ; Brockmann, K.DZNE* ; Svoboda, H. ; Trundell, D. ; Monnet, A. ; Doody, R. ; Fontoura, P. ; Kerchner, G. A. ; Brundin, P. ; Nikolcheva, T. ; Bonni, A. ; Investigators, P. (Collaboration Author) ; Group, P. S. (Collaboration Author)

2024
Nature America Inc. New York, NY

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Please use a persistent id in citations: doi:10.1038/s41591-024-02886-y

Abstract: Prasinezumab, a monoclonal antibody that binds aggregated α-synuclein, is being investigated as a potential disease-modifying therapy in early-stage Parkinson's disease. Although in the PASADENA phase 2 study, the primary endpoint (Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) sum of Parts I + II + III) was not met, prasinezumab-treated individuals exhibited slower progression of motor signs than placebo-treated participants (MDS-UPDRS Part III). We report here an exploratory analysis assessing whether prasinezumab showed greater benefits on motor signs progression in prespecified subgroups with faster motor progression. Prasinezumab's potential effects on disease progression were assessed in four prespecified and six exploratory subpopulations of PASADENA: use of monoamine oxidase B inhibitors at baseline (yes versus no); Hoehn and Yahr stage (2 versus 1); rapid eye movement sleep behavior disorder (yes versus no); data-driven subphenotypes (diffuse malignant versus nondiffuse malignant); age at baseline (≥60 years versus <60 years); sex (male versus female); disease duration (>12 months versus <12 months); age at diagnosis (≥60 years versus <60 years); motor subphenotypes (akinetic-rigid versus tremor-dominant); and motor subphenotypes (postural instability gait dysfunction versus tremor-dominant). In these subpopulations, the effect of prasinezumab on slowing motor signs progression (MDS-UPDRS Part III) was greater in the rapidly progressing subpopulations (for example, participants who were diffuse malignant or taking monoamine oxidase B inhibitors at baseline). This exploratory analysis suggests that, in a trial of 1-year duration, prasinezumab might reduce motor progression to a greater extent in individuals with more rapidly progressing Parkinson's disease. However, because this was a post hoc analysis, additional randomized clinical trials are needed to validate these findings.

Keyword(s): Humans (MeSH) ; Male (MeSH) ; Female (MeSH) ; Middle Aged (MeSH) ; Parkinson Disease (MeSH) ; Tremor: drug therapy (MeSH) ; Antiparkinson Agents: therapeutic use (MeSH) ; Monoamine Oxidase: therapeutic use (MeSH) ; Disease Progression (MeSH) ; Antiparkinson Agents ; Monoamine Oxidase

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Contributing Institute(s):

1. Parkinson Genetics (AG Gasser)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2024

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 80 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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