269254 20240428003926.0 10.1038/s41591-024-02886-y doi pmid:38622249 pmid pmc:PMC11031390 pmc 1078-8956 ISSN 1546-170X ISSN altmetric:162463438 altmetric DZNE-2024-00502 English 610 Pagano, Gennaro 0000-0002-6247-8988 0 Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson's disease. New York, NY 2024 Nature America Inc. article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1714043793_4332 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote 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. 353 - Clinical and Health Care Research (POF4-353) G:(DE-HGF)POF4-353 POF4-353 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de Antiparkinson Agents NLM Chemicals Monoamine Oxidase EC 1.4.3.4 NLM Chemicals 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 Taylor, Kirsten I 1 Anzures Cabrera, Judith 2 Simuni, Tanya 3 Marek, Kenneth 4 Postuma, Ronald B 5 Pavese, Nicola 6 Stocchi, Fabrizio 7 Brockmann, Kathrin P:(DE-2719)2811916 8 Svoboda, Hanno 9 Trundell, Dylan 10 Monnet, Annabelle 11 Doody, Rachelle 12 Fontoura, Paulo 13 Kerchner, Geoffrey A 14 Brundin, Patrik 15 Nikolcheva, Tania 16 Bonni, Azad 17 Investigators, PASADENA 18 Collaboration Author Group, Prasinezumab Study 19 Collaboration Author 10.1038/s41591-024-02886-y Vol. 30, no. 4, p. 1096 - 1103 PERI:(DE-600)1484517-9 4 1096 - 1103 Nature medicine 30 2024 1078-8956 http://pub.dzne.de/record/269254/files/DZNE-2024-00502%20SUP1.pdf http://pub.dzne.de/record/269254/files/DZNE-2024-00502%20SUP2.pdf OpenAccess http://pub.dzne.de/record/269254/files/DZNE-2024-00502.pdf pdfa http://pub.dzne.de/record/269254/files/DZNE-2024-00502%20SUP1.pdf?subformat=pdfa pdfa http://pub.dzne.de/record/269254/files/DZNE-2024-00502%20SUP2.pdf?subformat=pdfa OpenAccess pdfa http://pub.dzne.de/record/269254/files/DZNE-2024-00502.pdf?subformat=pdfa oai:pub.dzne.de:269254 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 8 P:(DE-2719)2811916 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-353 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Clinical and Health Care Research 0 2024 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2023-08-29 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2023-08-29 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2023-08-29 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2023-08-29 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2023-08-29 JCR StatID:(DE-HGF)0100 StatID NAT MED : 2022 2023-08-29 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2023-08-29 DEAL Nature StatID:(DE-HGF)3003 StatID 2023-08-29 ger DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2023-08-29 OpenAccess StatID:(DE-HGF)0510 StatID Creative Commons Attribution CC BY 4.0 LIC:(DE-HGF)CCBY4 HGFVOC Peer Review StatID:(DE-HGF)0030 StatID ASC 2023-08-29 IF >= 80 StatID:(DE-HGF)9980 StatID NAT MED : 2022 2023-08-29 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2023-08-29 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2023-08-29 DBCoverage StatID:(DE-HGF)1110 StatID Current Contents - Clinical Medicine 2023-08-29 Nationallizenz StatID:(DE-HGF)0420 StatID 2023-08-29 ger DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2023-08-29 I:(DE-2719)1210000 AG Gasser Parkinson Genetics 0 journal VDB UNRESTRICTED I:(DE-2719)1210000 FullTexts