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000269254 1001_ $$00000-0002-6247-8988$$aPagano, Gennaro$$b0
000269254 245__ $$aPrasinezumab slows motor progression in rapidly progressing early-stage Parkinson's disease.
000269254 260__ $$aNew York, NY$$bNature America Inc.$$c2024
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000269254 520__ $$aPrasinezumab, 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.
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000269254 650_7 $$2NLM Chemicals$$aAntiparkinson Agents
000269254 650_7 $$0EC 1.4.3.4$$2NLM Chemicals$$aMonoamine Oxidase
000269254 650_2 $$2MeSH$$aHumans
000269254 650_2 $$2MeSH$$aMale
000269254 650_2 $$2MeSH$$aFemale
000269254 650_2 $$2MeSH$$aMiddle Aged
000269254 650_2 $$2MeSH$$aParkinson Disease
000269254 650_2 $$2MeSH$$aTremor: drug therapy
000269254 650_2 $$2MeSH$$aAntiparkinson Agents: therapeutic use
000269254 650_2 $$2MeSH$$aMonoamine Oxidase: therapeutic use
000269254 650_2 $$2MeSH$$aDisease Progression
000269254 7001_ $$aTaylor, Kirsten I$$b1
000269254 7001_ $$aAnzures Cabrera, Judith$$b2
000269254 7001_ $$aSimuni, Tanya$$b3
000269254 7001_ $$aMarek, Kenneth$$b4
000269254 7001_ $$aPostuma, Ronald B$$b5
000269254 7001_ $$aPavese, Nicola$$b6
000269254 7001_ $$aStocchi, Fabrizio$$b7
000269254 7001_ $$0P:(DE-2719)2811916$$aBrockmann, Kathrin$$b8
000269254 7001_ $$aSvoboda, Hanno$$b9
000269254 7001_ $$aTrundell, Dylan$$b10
000269254 7001_ $$aMonnet, Annabelle$$b11
000269254 7001_ $$aDoody, Rachelle$$b12
000269254 7001_ $$aFontoura, Paulo$$b13
000269254 7001_ $$aKerchner, Geoffrey A$$b14
000269254 7001_ $$aBrundin, Patrik$$b15
000269254 7001_ $$aNikolcheva, Tania$$b16
000269254 7001_ $$aBonni, Azad$$b17
000269254 7001_ $$aInvestigators, PASADENA$$b18$$eCollaboration Author
000269254 7001_ $$aGroup, Prasinezumab Study$$b19$$eCollaboration Author
000269254 773__ $$0PERI:(DE-600)1484517-9$$a10.1038/s41591-024-02886-y$$gVol. 30, no. 4, p. 1096 - 1103$$n4$$p1096 - 1103$$tNature medicine$$v30$$x1078-8956$$y2024
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