TY  - JOUR
AU  - Pagano, Gennaro
AU  - Taylor, Kirsten I
AU  - Anzures Cabrera, Judith
AU  - Simuni, Tanya
AU  - Marek, Kenneth
AU  - Postuma, Ronald B
AU  - Pavese, Nicola
AU  - Stocchi, Fabrizio
AU  - Brockmann, Kathrin
AU  - Svoboda, Hanno
AU  - Trundell, Dylan
AU  - Monnet, Annabelle
AU  - Doody, Rachelle
AU  - Fontoura, Paulo
AU  - Kerchner, Geoffrey A
AU  - Brundin, Patrik
AU  - Nikolcheva, Tania
AU  - Bonni, Azad
TI  - Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson's disease.
JO  - Nature medicine
VL  - 30
IS  - 4
SN  - 1078-8956
CY  - New York, NY
PB  - Nature America Inc.
M1  - DZNE-2024-00502
SP  - 1096 - 1103
PY  - 2024
AB  - 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.
KW  - Humans
KW  - Male
KW  - Female
KW  - Middle Aged
KW  - Parkinson Disease
KW  - Tremor: drug therapy
KW  - Antiparkinson Agents: therapeutic use
KW  - Monoamine Oxidase: therapeutic use
KW  - Disease Progression
KW  - Antiparkinson Agents (NLM Chemicals)
KW  - Monoamine Oxidase (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:38622249
C2  - pmc:PMC11031390
DO  - DOI:10.1038/s41591-024-02886-y
UR  - https://pub.dzne.de/record/269254
ER  -