Journal article
Neuronal alpha-Synuclein Disease integrated staging system performance in PPMI, PASADENA, and SPARK baseline cohorts
NPJ Parkinson's Disease, Vol.10(1), 178
09/27/2024
DOI: 10.1038/s41531-024-00789-w
PMCID: PMC11567150
PMID: 39333167
Abstract
The Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA, and SPARK studies, we developed and applied biologic and clinical data-informed definitions for the NSD-ISS across the disease continuum. Individuals enrolled as Parkinson's disease, Prodromal, or Healthy Controls were defined and staged based on biological, clinical, and functional anchors at baseline. Across the three studies 1741 participants had SAA data and of these 1030 (59%) were S+ consistent with NSD. Among sporadic PD, 683/736 (93%) were NSD, and the distribution for Stages 2B, 3, and 4 was 25%, 63%, and 9%, respectively. Median (95% CI) time to developing a clinically meaningful outcome was 8.3 (6.2, 10.1), 5.9 (4.1, 6.0), and 2.4 (1.0, 4.0) years for baseline stage 2B, 3, and 4, respectively. We propose pilot biologic and clinical anchors for NSD-ISS. Our results highlight the baseline heterogeneity of individuals currently defined as early PD. Baseline stage predicts time to progression to clinically meaningful milestones. Further research on validation of the anchors in longitudinal cohorts is necessary.
Details
- Title: Subtitle
- Neuronal alpha-Synuclein Disease integrated staging system performance in PPMI, PASADENA, and SPARK baseline cohorts
- Creators
- Tien Dam - BiogenGennaro Pagano - RocheMichael C Brumm - University of IowaCaroline Gochanour - University of IowaKathleen L Poston - Stanford UniversityDaniel Weintraub - University of PennsylvaniaLana M Chahine - University of PittsburghChristopher Coffey - University of IowaCaroline M Tanner - University of California, San FranciscoCatherine M Kopil - Michael J. Fox FoundationYuge Xiao - Michael J. Fox FoundationSohini Chowdhury - Michael J. Fox FoundationLuis Concha-Marambio - AmprionPeter DiBiaso - Clinical SolutionsTatiana Foroud - Indiana University – Purdue University IndianapolisMark Frasier - Michael J. Fox FoundationDanna Jennings - Denali TherapeuticsKarl Kieburtz - University of Rochester Medical CenterKalpana Merchant - Northwestern UniversityBrit Mollenhauer - Paracelsus Elena Klinik KasselThomas J Montine - Stanford UniversityKelly Nudelman - Indiana University – Purdue University IndianapolisJohn Seibyl - Institute for Neurodegenerative DisordersTodd Sherer - Michael J. Fox FoundationAndrew Singleton - National Institutes of HealthDiane Stephenson - Critical Path InstituteMatthew Stern - University of PennsylvaniaClaudio Soto - AmprionEduardo Tolosa - Universitat de BarcelonaAndrew Siderowf - University of PennsylvaniaBilly Dunn - Michael J. Fox FoundationTanya Simuni - Northwestern UniversityKenneth Marek - University of Rochester Medical CenterParkinson’s Progression Markers Initiative
- Resource Type
- Journal article
- Publication Details
- NPJ Parkinson's Disease, Vol.10(1), 178
- DOI
- 10.1038/s41531-024-00789-w
- PMID
- 39333167
- PMCID
- PMC11567150
- NLM abbreviation
- NPJ Parkinsons Dis
- ISSN
- 2373-8057
- eISSN
- 2373-8057
- Publisher
- NATURE PORTFOLIO
- Grant note
- Michael J. Fox Foundation for Parkinson's Research (MJFF)Michael J. Fox Foundation for Parkinson's Research (MJFF)F. Hoffman-La RocheF. Hoffman-La RocheProthena Biosciences, SPARKProthena Biosciences, SPARKBiogenBiogenPPMI - Avid RadiopharmaceuticalsPPMI - Avid RadiopharmaceuticalsBIALBIALEdmond J. Safra FoundationEdmond J. Safra FoundationEli Lilly, Gain TherapeuticsEli Lilly, Gain TherapeuticsGE HealthCareGE HealthCareLundbeckLundbeckMeso Scale Discovery, Mission TherapeuticsMeso Scale Discovery, Mission TherapeuticsNeurocrine BiosciencesNeurocrine BiosciencesRocheRocheSun Pharma Advanced Research CompanySun Pharma Advanced Research CompanyTakedaTakedaTevaTevaVoyager TherapeuticsVoyager TherapeuticsWeston Family Foundation: 2023, RRID:SCR 006431 Weston Family Foundation
We appreciate Dr. Teresa Buraccio for critical review of the draft of the manuscript. We thank the SPARK investigators, trial coordinators, staff, and participants for their contribution to the trial. We appreciate Dr. Minhua Yang for analyses of the SPARK data. We thank the PASADENA investigators, trial coordinators, staff, and participants for their contribution to the trial. We appreciate Drs. Thomas Riorge and Annabelle Monnet for analyses of the PASADENA data. Sources of funding Funding support for the data analysis was provided by The Michael J. Fox Foundation for Parkinson's Research (MJFF). This report presents data from three studies, including PASADENA, supported by F. Hoffman-La Roche and Prothena Biosciences, SPARK, supported by Biogen, and PPMI. PPMI-a public-private partnership-is funded by MJFF and funding partners, including 4D Pharma, Abbvie, AcureX, Allergan, Amathus Therapeutics, Aligning Science Across Parkinson's, AskBio, Avid Radiopharmaceuticals, BIAL, BioArctic, Biogen, Biohaven, BioLegend, BlueRock Therapeutics, BristolMyers Squibb, Calico Labs, Capsida Biotherapeutics, Celgene, Cerevel Therapeutics, Coave Therapeutics, DaCapo Brainscience, Denali, Edmond J. Safra Foundation, Eli Lilly, Gain Therapeutics, GE HealthCare, Genentech, GSK, Golub Capital, Handl Therapeutics, Insitro, Janssen Neuroscience, Jazz Pharmaceuticals, Lundbeck, Merck, Meso Scale Discovery, Mission Therapeutics, Neurocrine Biosciences, Neuropore, Pfizer, Piramal, Prevail Therapeutics, Roche, Sanofi, Servier, Sun Pharma Advanced Research Company, Takeda, Teva, UCB, Vanqua Bio, Verily, Voyager Therapeutics, the Weston Family Foundation and Yumanity Therapeutics. Role of the funding source Research officers (SC, MF, CK, TS, YX) at MJFF, PPMI Sponsor, were involved in the design of the study and writing of the manuscript. Data source PPMI data used in the preparation of this article were obtained June 12, 2023 from the Parkinson's Progression Markers Initiative (PPMI) database (www.ppmi-info.org/access-data-specimens/download-data), RRID:SCR 006431. For up-to-date information on the study, visit www.ppmi-info.org.
- Language
- English
- Date published
- 09/27/2024
- Academic Unit
- Biostatistics
- Record Identifier
- 9984721239102771
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