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Record W4403228604 · doi:10.1038/s41591-024-03270-6

Sustained effect of prasinezumab on Parkinson’s disease motor progression in the open-label extension of the PASADENA trial

2024· article· en· W4403228604 on OpenAlexafffund
Gennaro Pagano, Annabelle Monnet, Benjamin Ribba, Hanno Svoboda, Thomas Kustermann, Tanya Simuni, Ronald B. Postuma, Nicola Pavese, Fabrizio Stocchi, Kathrin Brockmann, Krzysztof Śmigórski, Valentina Gerbaldo, Paulo Fontoura, Rachelle S. Doody, Geoffrey A. Kerchner, Patrik Brundin, Kenneth Marek, Azad Bonni, Tania Nikolcheva

Bibliographic record

VenueNature Medicine · 2024
Typearticle
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
FundersSanofi GenzymeFeinberg School of MedicineAllerganGenentechNational Institutes of HealthMitsubishi Tanabe Pharma CorporationServierEisaiNewcastle UniversityUniversity of ExeterParkinson's UKVoyager TherapeuticsJazz PharmaceuticalsProthenaDenali TherapeuticsNeurocrine BiosciencesWeston Brain InstituteH. Lundbeck A/SDeutsches Zentrum für Neurodegenerative ErkrankungenSunovionDeutsche ForschungsgemeinschaftRocheMcGill UniversityMichael J. Fox Foundation for Parkinson's ResearchBoston Scientific CorporationPfizerNorthwestern UniversityBiogenParkinson's FoundationCelgeneVerily Life SciencesTeva Pharmaceutical IndustriesSanofiParkinson CanadaF. Hoffmann-La RocheGlaxoSmithKlineEli Lilly and CompanyBristol-Myers Squibb
KeywordsPlaceboParkinson's diseaseMedicineRating scaleInternal medicineLevodopaDiseaseMotor symptomsPsychologyPhysical therapyPhysical medicine and rehabilitationPathology

Abstract

fetched live from OpenAlex

The Phase II trial of Anti-alpha-Synuclein Antibody in Early Parkinson's Disease (PASADENA) is an ongoing double-blind, placebo-controlled trial evaluating the safety and efficacy of prasinezumab in early-stage Parkinson's disease (PD). During the double-blind period, prasinezumab-treated individuals showed less progression of motor signs (Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III) than placebo-treated individuals. We evaluated whether the effect of prasinezumab on motor progression, assessed as a change in MDS-UPDRS Part III score in the OFF and ON states, and MDS-UPDRS Part II score, was sustained for 4 years from the start of the trial. We compared participants enrolled in the PASADENA open-label extension study with those enrolled in an external comparator arm derived from the Parkinson's Progression Markers Initiative observational study. The PASADENA delayed-start (n = 94) and early-start (n = 177) groups showed a slower decline (a smaller increase in score) in MDS-UPDRS Part III scores in the OFF state (delayed start, -51%; early start, -65%), ON state (delayed start, -94%; early start, -118%) and MDS-UPDRS Part II (delayed start, -48%; early start, -40%) than did the Parkinson's Progression Markers Initiative external comparator (n = 303). This exploratory analysis, which requires confirmation in future studies, suggested that the effect of prasinezumab in slowing motor progression in PD may be sustained long term. PASADENA ClinicalTrials.gov no. NCT03100149 .

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)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.262
Threshold uncertainty score0.434

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
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 head0.018
GPT teacher head0.359
Teacher spread0.341 · 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.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
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

Citations48
Published2024
Admission routes2
Has abstractyes

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