000909580 001__ 909580 000909580 005__ 20240109115058.0 000909580 0247_ $$2doi$$a10.1056/NEJMoa2202867 000909580 0247_ $$2ISSN$$a0028-4793 000909580 0247_ $$2ISSN$$a1533-4406 000909580 0247_ $$2datacite_doi$$a10.34734/FZJ-2022-03262 000909580 0247_ $$2pmid$$a35921451 000909580 0247_ $$2WOS$$aWOS:000861612100008 000909580 037__ $$aFZJ-2022-03262 000909580 082__ $$a610 000909580 1001_ $$0P:(DE-HGF)0$$aPagano, Gennaro$$b0$$eCorresponding author 000909580 245__ $$aTrial of Prasinezumab in Early-Stage Parkinson’s Disease 000909580 260__ $$aWaltham, Mass.$$bMMS$$c2022 000909580 3367_ $$2DRIVER$$aarticle 000909580 3367_ $$2DataCite$$aOutput Types/Journal article 000909580 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1702800103_26669 000909580 3367_ $$2BibTeX$$aARTICLE 000909580 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000909580 3367_ $$00$$2EndNote$$aJournal Article 000909580 520__ $$aBackground: Aggregated α-synuclein plays an important role in the pathogenesis of Parkinson's disease. The monoclonal antibody prasinezumab, directed at aggregated α-synuclein, is being studied for its effect on Parkinson's disease.Methods: In this phase 2 trial, we randomly assigned participants with early-stage Parkinson's disease in a 1:1:1 ratio to receive intravenous placebo or prasinezumab at a dose of 1500 mg or 4500 mg every 4 weeks for 52 weeks. The primary end point was the change from baseline to week 52 in the sum of scores on parts I, II, and III of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 236, with higher scores indicating greater impairment). Secondary end points included the dopamine transporter levels in the putamen of the hemisphere ipsilateral to the clinically more affected side of the body, as measured by 123I-ioflupane single-photon-emission computed tomography (SPECT).Results: A total of 316 participants were enrolled; 105 were assigned to receive placebo, 105 to receive 1500 mg of prasinezumab, and 106 to receive 4500 mg of prasinezumab. The baseline mean MDS-UPDRS scores were 32.0 in the placebo group, 31.5 in the 1500-mg group, and 30.8 in the 4500-mg group, and mean (±SE) changes from baseline to 52 weeks were 9.4±1.2 in the placebo group, 7.4±1.2 in the 1500-mg group (difference vs. placebo, -2.0; 80% confidence interval [CI], -4.2 to 0.2; P = 0.24), and 8.8±1.2 in the 4500-mg group (difference vs. placebo, -0.6; 80% CI, -2.8 to 1.6; P = 0.72). There was no substantial difference between the active-treatment groups and the placebo group in dopamine transporter levels on SPECT. The results for most clinical secondary end points were similar in the active-treatment groups and the placebo group. Serious adverse events occurred in 6.7% of the participants in the 1500-mg group and in 7.5% of those in the 4500-mg group; infusion reactions occurred in 19.0% and 34.0%, respectively.Conclusions: Prasinezumab therapy had no meaningful effect on global or imaging measures of Parkinson's disease progression as compared with placebo and was associated with infusion reactions. (Funded by F. Hoffmann-La Roche and Prothena Biosciences; PASADENA ClinicalTrials.gov number, NCT03100149.). 000909580 536__ $$0G:(DE-HGF)POF4-5251$$a5251 - Multilevel Brain Organization and Variability (POF4-525)$$cPOF4-525$$fPOF IV$$x0 000909580 536__ $$0G:(DE-HGF)POF4-5253$$a5253 - Neuroimaging (POF4-525)$$cPOF4-525$$fPOF IV$$x1 000909580 588__ $$aDataset connected to CrossRef, Journals: juser.fz-juelich.de 000909580 7001_ $$0P:(DE-HGF)0$$aTaylor, Kirsten I.$$b1 000909580 7001_ $$0P:(DE-HGF)0$$aAnzures-Cabrera, Judith$$b2 000909580 7001_ $$0P:(DE-HGF)0$$aMarchesi, Maddalena$$b3 000909580 7001_ $$0P:(DE-HGF)0$$aSimuni, Tanya$$b4 000909580 7001_ $$0P:(DE-HGF)0$$aMarek, Kenneth$$b5 000909580 7001_ $$0P:(DE-HGF)0$$aPostuma, Ronald B.$$b6 000909580 7001_ $$0P:(DE-HGF)0$$aPavese, Nicola$$b7 000909580 7001_ $$0P:(DE-HGF)0$$aStocchi, Fabrizio$$b8 000909580 7001_ $$0P:(DE-HGF)0$$aAzulay, Jean-Philippe$$b9 000909580 7001_ $$0P:(DE-HGF)0$$aMollenhauer, Brit$$b10 000909580 7001_ $$0P:(DE-HGF)0$$aLópez-Manzanares, Lydia$$b11 000909580 7001_ $$0P:(DE-HGF)0$$aRussell, David S.$$b12 000909580 7001_ $$0P:(DE-HGF)0$$aBoyd, James T.$$b13 000909580 7001_ $$0P:(DE-HGF)0$$aNicholas, Anthony P.$$b14 000909580 7001_ $$0P:(DE-HGF)0$$aLuquin, María R.$$b15 000909580 7001_ $$0P:(DE-HGF)0$$aHauser, Robert A.$$b16 000909580 7001_ $$0P:(DE-HGF)0$$aGasser, Thomas$$b17 000909580 7001_ $$0P:(DE-HGF)0$$aPoewe, Werner$$b18 000909580 7001_ $$0P:(DE-HGF)0$$aRicci, Benedicte$$b19 000909580 7001_ $$0P:(DE-HGF)0$$aBoulay, Anne$$b20 000909580 7001_ $$0P:(DE-HGF)0$$aVogt, Annamarie$$b21 000909580 7001_ $$0P:(DE-HGF)0$$aBoess, Frank G.$$b22 000909580 7001_ $$0P:(DE-Juel1)177727$$aDukart, Jürgen$$b23$$ufzj 000909580 7001_ $$0P:(DE-HGF)0$$aD’Urso, Giulia$$b24 000909580 7001_ $$0P:(DE-HGF)0$$aFinch, Rebecca$$b25 000909580 7001_ $$0P:(DE-HGF)0$$aZanigni, Stefano$$b26 000909580 7001_ $$0P:(DE-HGF)0$$aMonnet, Annabelle$$b27 000909580 7001_ $$0P:(DE-HGF)0$$aPross, Nathalie$$b28 000909580 7001_ $$0P:(DE-HGF)0$$aHahn, Andrea$$b29 000909580 7001_ $$0P:(DE-HGF)0$$aSvoboda, Hanno$$b30 000909580 7001_ $$0P:(DE-HGF)0$$aBritschgi, Markus$$b31 000909580 7001_ $$0P:(DE-HGF)0$$aLipsmeier, Florian$$b32 000909580 7001_ $$0P:(DE-HGF)0$$aVolkova-Volkmar, Ekaterina$$b33 000909580 7001_ $$0P:(DE-HGF)0$$aLindemann, Michael$$b34 000909580 7001_ $$0P:(DE-HGF)0$$aDziadek, Sebastian$$b35 000909580 7001_ $$0P:(DE-HGF)0$$aHoliga, Štefan$$b36 000909580 7001_ $$0P:(DE-HGF)0$$aRukina, Daria$$b37 000909580 7001_ $$0P:(DE-HGF)0$$aKustermann, Thomas$$b38 000909580 7001_ $$0P:(DE-HGF)0$$aKerchner, Geoffrey A.$$b39 000909580 7001_ $$0P:(DE-HGF)0$$aFontoura, Paulo$$b40 000909580 7001_ $$0P:(DE-HGF)0$$aUmbricht, Daniel$$b41 000909580 7001_ $$0P:(DE-HGF)0$$aDoody, Rachelle$$b42 000909580 7001_ $$0P:(DE-HGF)0$$aNikolcheva, Tania$$b43 000909580 7001_ $$0P:(DE-HGF)0$$aBonni, Azad$$b44 000909580 773__ $$0PERI:(DE-600)1468837-2$$a10.1056/NEJMoa2202867$$gVol. 387, no. 5, p. 421 - 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