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Record W4394822077 · doi:10.1038/s41591-024-02886-y

Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson’s disease

2024· article· en· W4394822077 on OpenAlexaff
Gennaro Pagano, Kirsten I. Taylor, Judith Anzures Cabrera, Tanya Simuni, Kenneth Marek, Ronald B. Postuma, Nicola Pavese, Fabrizio Stocchi, Kathrin Brockmann, Hanno Svoboda, Dylan Trundell, Annabelle Monnet, Rachelle S. Doody, Paulo Fontoura, Geoffrey A. Kerchner, Patrik Brundin, Tania Nikolcheva, Azad Bonni

Bibliographic record

VenueNature Medicine · 2024
Typearticle
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
FundersF. Hoffmann-La RocheRoche
KeywordsParkinson's diseaseInternal medicineSelegilineDiseaseMedicinePsychologyMovement disordersRating scalePlaceboOncologyPathology

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.554
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.327
Teacher spread0.314 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations116
Published2024
Admission routes1
Has abstractyes

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