% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Pagano:165174, author = {Pagano, Gennaro and Taylor, Kirsten I and Anzures-Cabrera, Judith and Marchesi, Maddalena and Simuni, Tanya and Marek, Kenneth and Postuma, Ronald B and Pavese, Nicola and Stocchi, Fabrizio and Azulay, Jean-Philippe and Mollenhauer, Brit and López-Manzanares, Lydia and Russell, David S and Boyd, James T and Nicholas, Anthony P and Luquin, María R and Hauser, Robert A and Gasser, Thomas and Poewe, Werner and Ricci, Benedicte and Boulay, Anne and Vogt, Annamarie and Boess, Frank G and Dukart, Juergen and D'Urso, Giulia and Finch, Rebecca and Zanigni, Stefano and Monnet, Annabelle and Pross, Nathalie and Hahn, Andrea and Svoboda, Hanno and Britschgi, Markus and Lipsmeier, Florian and Volkova-Volkmar, Ekaterina and Lindemann, Michael and Dziadek, Sebastian and Holiga, Štefan and Rukina, Daria and Kustermann, Thomas and Kerchner, Geoffrey A and Fontoura, Paulo and Umbricht, Daniel and Doody, Rachelle and Nikolcheva, Tania and Bonni, Azad}, collaboration = {Investigators, PASADENA and Group, Prasinezumab Study}, title = {{T}rial of {P}rasinezumab in {E}arly-{S}tage {P}arkinson's {D}isease.}, journal = {The New England journal of medicine}, volume = {387}, number = {5}, issn = {0028-4793}, address = {Waltham, Mass.}, publisher = {MMS}, reportid = {DZNE-2022-01476}, pages = {421 - 432}, year = {2022}, abstract = {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.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).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.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.).}, keywords = {Antibodies, Monoclonal, Humanized: therapeutic use / Antiparkinson Agents: therapeutic use / Dopamine Plasma Membrane Transport Proteins: therapeutic use / Double-Blind Method / Humans / Parkinson Disease: drug therapy / Treatment Outcome / alpha-Synuclein: antagonists $\&$ inhibitors / Antibodies, Monoclonal, Humanized (NLM Chemicals) / Antiparkinson Agents (NLM Chemicals) / Dopamine Plasma Membrane Transport Proteins (NLM Chemicals) / alpha-Synuclein (NLM Chemicals)}, cin = {AG Gasser}, ddc = {610}, cid = {I:(DE-2719)1210000}, pnm = {353 - Clinical and Health Care Research (POF4-353)}, pid = {G:(DE-HGF)POF4-353}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:35921451}, doi = {10.1056/NEJMoa2202867}, url = {https://pub.dzne.de/record/165174}, }