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@ARTICLE{Pagano:269254,
      author       = {Pagano, Gennaro and Taylor, Kirsten I and Anzures Cabrera,
                      Judith and Simuni, Tanya and Marek, Kenneth and Postuma,
                      Ronald B and Pavese, Nicola and Stocchi, Fabrizio and
                      Brockmann, Kathrin and Svoboda, Hanno and Trundell, Dylan
                      and Monnet, Annabelle and Doody, Rachelle and Fontoura,
                      Paulo and Kerchner, Geoffrey A and Brundin, Patrik and
                      Nikolcheva, Tania and Bonni, Azad},
      collaboration = {Investigators, PASADENA and Group, Prasinezumab Study},
      title        = {{P}rasinezumab slows motor progression in rapidly
                      progressing early-stage {P}arkinson's disease.},
      journal      = {Nature medicine},
      volume       = {30},
      number       = {4},
      issn         = {1078-8956},
      address      = {New York, NY},
      publisher    = {Nature America Inc.},
      reportid     = {DZNE-2024-00502},
      pages        = {1096 - 1103},
      year         = {2024},
      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.},
      keywords     = {Humans / Male / Female / Middle Aged / Parkinson Disease /
                      Tremor: drug therapy / Antiparkinson Agents: therapeutic use
                      / Monoamine Oxidase: therapeutic use / Disease Progression /
                      Antiparkinson Agents (NLM Chemicals) / Monoamine Oxidase
                      (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:38622249},
      pmc          = {pmc:PMC11031390},
      doi          = {10.1038/s41591-024-02886-y},
      url          = {https://pub.dzne.de/record/269254},
}