2024
Cinpanemab in Early Parkinson Disease: Evaluation of Biomarker Results From the Phase 2 SPARK Clinical Trial.
Hutchison R, Fraser K, Yang M, Fox T, Hirschhorn E, Njingti E, Scott D, Bedell B, Kistner K, Cedarbaum J, Evans K, Graham D, Martarello L, Mollenhauer B, Lang A, Dam T, Beaver J. Cinpanemab in Early Parkinson Disease: Evaluation of Biomarker Results From the Phase 2 SPARK Clinical Trial. Neurology 2024, 102: e209137. PMID: 38315945, DOI: 10.1212/wnl.0000000000209137.Peer-Reviewed Original ResearchConceptsDisease progressionDopaminergic deficitNeurofilament light chain levelsNigrostriatal dopamine pathwayDopamine transporter SPECTTerminated due to lackStriatal dopaminergic deficitsLight chain levelsClinical disease progressionEvidence of dopaminergic deficitParkinson's diseaseEvaluate disease severityBiomarker measurementsEarly Parkinson's diseaseStriatal binding ratiosDevelopment of therapiesStatistically significant differenceScale total scoreBiomarker resultsDouble-blindPlacebo-controlledUnified Parkinson's Disease Rating Scale total scoreDopamine pathwayClinical trialsPrimary outcome
2021
Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial
Hutchison R, Evans K, Fox T, Yang M, Barakos J, Bedell B, Cedarbaum J, Brys M, Siderowf A, Lang A. Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial. BMC Neurology 2021, 21: 459. PMID: 34814867, PMCID: PMC8609885, DOI: 10.1186/s12883-021-02470-8.Peer-Reviewed Original ResearchConceptsDAT-SPECTParkinson's diseaseClinical trialsDisease trialsPhase 2 trialDopaminergic nerve terminalsEarly Parkinson's diseaseDisease-modifying therapiesIdiopathic Parkinson's diseaseMulticenter clinical trialParkinson's disease trialStudy design aspectsSingle photon emissionStages of progressionDegenerative parkinsonismEnrichment biomarkerResultsIn totalClinical assessmentNerve terminalsBlinded neuroradiologistsClinical diagnosisDopamine transporterMonoclonal antibodiesCentral laboratoryTrialsSeeking progress in disease modification in Parkinson disease
Lungu C, Cedarbaum J, Dawson T, Dorsey E, Faraco C, Federoff H, Fiske B, Fox R, Goldfine A, Kieburtz K, Macklin E, Matthews H, Rafaloff G, Saunders-Pullman R, Schor N, Schwarzschild M, Sieber B, Simuni T, Surmeier D, Tamiz A, Werner M, Wright C, Wyse R. Seeking progress in disease modification in Parkinson disease. Parkinsonism & Related Disorders 2021, 90: 134-141. PMID: 34561166, DOI: 10.1016/j.parkreldis.2021.09.006.Peer-Reviewed Original ResearchConceptsDisease modificationParkinson's diseaseDisease-modifying benefitsNovel trial designsDrug therapyPatient populationTrial failuresTherapeutic targetTrial designNeurological disordersRelevant biomarkersTherapeutic developmentNational InstituteDiseaseReview articleResearch prioritiesKey stakeholder groupsFailureLikelihood of successTherapyStrokeBiomarkersSystematic Assessment of 10 Biomarker Candidates Focusing on α‐Synuclein‐Related Disorders
Schulz I, Kruse N, Gera R, Kremer T, Cedarbaum J, Barbour R, Zago W, Schade S, Otte B, Bartl M, Hutten S, Trenkwalder C, Mollenhauer B. Systematic Assessment of 10 Biomarker Candidates Focusing on α‐Synuclein‐Related Disorders. Movement Disorders 2021, 36: 2874-2887. PMID: 34363416, DOI: 10.1002/mds.28738.Peer-Reviewed Original ResearchConceptsGlial fibrillary acidic proteinCerebrospinal fluidChitinase-3-like protein 1Calcium-binding protein BUbiquitin C-terminal hydrolase L1Myeloid cells 2Neurofilament light chainObjective diagnostic biomarkersFibrillary acidic proteinNeurofilament heavy chainDiagnostic biomarker candidatesDiagnostic biomarkersClinical diagnosisTau proteinPhosphorylated aSynNeurodegenerative disordersAcidic proteinCells 2Α-synucleinBiomarker candidatesProtein 1Candidate markersAvailable kitsDisordersLight chainMutations in GBA and LRRK2 Are Not Associated with Increased Inflammatory Markers
Thaler A, Omer N, Giladi N, Gurevich T, Bar-Shira A, Gana-Weisz M, Goldstein O, Kestenbaum M, Shirvan J, Cedarbaum J, Orr-Urtreger A, Regev K, Shenhar-Tsarfaty S, Mirelman A. Mutations in GBA and LRRK2 Are Not Associated with Increased Inflammatory Markers. Journal Of Parkinson's Disease 2021, 11: 1285-1296. PMID: 33998549, PMCID: PMC8461659, DOI: 10.3233/jpd-212624.Peer-Reviewed Original ResearchConceptsNon-manifesting carriersRole of inflammationGBA-PDParkinson's diseaseGenetic Parkinson's diseaseLRRK2-PDPD patientsCerebrospinal fluidNon-manifesting mutation carriersAnti-inflammatory treatmentProdromal Parkinson's diseaseGeneral medical conditionsIdiopathic Parkinson's diseaseLRRK2-PD patientsCSF cytokinesGBA-NMCLRRK2-NMCPeripheral cytokinesInflammatory markersIL-10Inflammatory measuresDisease characteristicsIL-1βIL-6Peripheral bloodLongitudinal Changes in Neuromelanin MRI Signal in Parkinson's Disease: A Progression Marker
Gaurav R, Yahia‐Cherif L, Pyatigorskaya N, Mangone G, Biondetti E, Valabrègue R, Ewenczyk C, Hutchison R, Cedarbaum J, Corvol J, Vidailhet M, Lehéricy S. Longitudinal Changes in Neuromelanin MRI Signal in Parkinson's Disease: A Progression Marker. Movement Disorders 2021, 36: 1592-1602. PMID: 33751655, PMCID: PMC8359265, DOI: 10.1002/mds.28531.Peer-Reviewed Original ResearchConceptsTotal intracranial volumePD patientsHealthy volunteersParkinson's diseaseIntracranial volumeObservational case-control studySubstantia nigra pars compactaDirect noninvasive assessmentDisease-modifying treatmentsEarly PD patientsFemale PD patientsTherapeutic drug trialsCase-control studyNeuromelanin-sensitive MRI techniquesNeuromelanin-sensitive imagingMale patientsFemale patientsPars compactaCohort IICohort IDrug trialsPatientsImaging biomarkersNoninvasive assessmentDisease severityBiochemical markers for severity and risk in GBA and LRRK2 Parkinson’s disease
Thaler A, Omer N, Giladi N, Gurevich T, Bar-Shira A, Gana-Weisz M, Goldstein O, Kestenbaum M, Cedarbaum J, Orr-Urtreger A, Shenhar-Tsarfaty S, Mirelman A. Biochemical markers for severity and risk in GBA and LRRK2 Parkinson’s disease. Journal Of Neurology 2021, 268: 1517-1525. PMID: 33388928, DOI: 10.1007/s00415-020-10325-4.Peer-Reviewed Original ResearchConceptsNon-manifesting carriersProdromal Parkinson's diseaseWhite blood countParkinson's diseaseMicroalbumin/creatinine ratioNeutrophil/lymphocyte ratioGBA-PD patientsWorse motor performanceGlomerular filtration rateLRRK2 mutation carriersC-reactive proteinIdiopathic Parkinson's diseaseGBA-NMCGBA-PDLRRK2-NMCCreatinine ratioLRRK2-PDLymphocyte ratioVitamin DBlood countFiltration rateIdiopathic PDMutation carriersPD severityBiochemical markers
2020
Disease modification and biomarker development in Parkinson disease: Revision or reconstruction?
Espay A, Kalia L, Gan-Or Z, Williams-Gray C, Bedard P, Rowe S, Morgante F, Fasano A, Stecher B, Kauffman M, Farrer M, Coffey C, Schwarzschild M, Sherer T, Postuma R, Strafella A, Singleton A, Barker R, Kieburtz K, Olanow C, Lozano A, Kordower J, Cedarbaum J, Brundin P, Standaert D, Lang A. Disease modification and biomarker development in Parkinson disease: Revision or reconstruction? Neurology 2020, 94: 481-494. PMID: 32102975, PMCID: PMC7220234, DOI: 10.1212/wnl.0000000000009107.Peer-Reviewed Original ResearchConceptsClinicopathologic modelDisease modificationDisease-modifying interventionsParkinson's disease researchCommon pathobiologyLewy neuritesLewy bodiesIdiopathic formClinical trialsPostmortem studiesBreast cancerParkinson's diseaseCystic fibrosisSingle disorderΑ-synucleinBiomarker developmentSmall subgroupGenetic PDDiseaseTrial effortsBiomarkersUnique entityCohortTrue failuresDisease research
2019
The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease
Stephenson D, Hill D, Cedarbaum JM, Tome M, Vamvakas S, Romero K, Conrado DJ, Dexter DT, Seibyl J, Jennings D, Nicholas T, Matthews D, Xie Z, Imam S, Maguire P, Russell D, Gordon MF, Stebbins GT, Somer E, Gallagher J, Roach A, Basseches P, Grosset D, Marek K, Consortium O. The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease. Journal Of Parkinson's Disease 2019, 9: 553-563. PMID: 31306141, PMCID: PMC6700608, DOI: 10.3233/jpd-191648.Peer-Reviewed Original ResearchConceptsEuropean Medicines AgencyParkinson's diseaseDopamine transporterEnrichment biomarkerClinical trialsPD subjectsParkinson's Progression Markers Initiative (PPMI) studyMotor Parkinson's diseaseParkinson Research ExaminationStriatal DAT bindingUPDRS part IISingle photon emission tomographyAppropriate patient selectionEarly Parkinson's diseaseIdiopathic PD patientsClinical trial populationsFuture clinical trialsClinical trial dataPhoton emission tomographyEarly motor symptomsTest therapeuticsIndependent predictorsTherapeutic trialsDopaminergic deficitMotor symptomsMolecular Neuroimaging of the Dopamine Transporter as a Patient Enrichment Biomarker for Clinical Trials for Early Parkinson's Disease
Romero K, Conrado D, Burton J, Nicholas T, Sinha V, Macha S, Ahamadi M, Cedarbaum J, Seibyl J, Marek K, Basseches P, Hill D, Somer E, Gallagher J, Dexter DT, Roach A, Stephenson D, Consortium F, Initiative T. Molecular Neuroimaging of the Dopamine Transporter as a Patient Enrichment Biomarker for Clinical Trials for Early Parkinson's Disease. Clinical And Translational Science 2019, 12: 240-246. PMID: 30706986, PMCID: PMC6510371, DOI: 10.1111/cts.12619.Peer-Reviewed Original ResearchConceptsClinical trialsImaging biomarkersDopamine transporterEuropean Medicines Agency's CommitteeParkinson's disease clinical trialsEarly Parkinson's diseaseCritical Path InstitutePatient selectionEnrichment biomarkerParkinson's diseaseMolecular neuroimagingPharmaceutical partnersDiseaseBiomarkersTrialsQualification opinionHuman useInternational ConsortiumTransportersMedical productsNeuroimagingA Proposed Roadmap for Parkinson’s Disease Proof of Concept Clinical Trials Investigating Compounds Targeting Alpha-Synuclein
Merchant KM, Cedarbaum JM, Brundin P, Dave KD, Eberling J, Espay AJ, Hutten SJ, Javidnia M, Luthman J, Maetzler W, Menalled L, Reimer AN, Stoessl AJ, Weiner DM, . A Proposed Roadmap for Parkinson’s Disease Proof of Concept Clinical Trials Investigating Compounds Targeting Alpha-Synuclein. Journal Of Parkinson's Disease 2019, Preprint: 1-31. PMID: 30400107, PMCID: PMC6398545, DOI: 10.3233/jpd-181471.Peer-Reviewed Original ResearchConceptsParkinson's diseaseProgression of PDDisease-modifying therapiesConcept clinical trialMichael J. Fox FoundationDisease-modifying therapeuticsLewy pathologyClinical outcomesClinical trialsTargeting therapyAnimal modelsClinical proofAlpha-synucleinBiomarker toolkitΑ-synClinical researchInvestigational moleculesTherapyPD researchTranslational frameworkParkinson's ResearchDiseaseBiomarkersConcept studyMeaningful stridesFeasibility and safety of lumbar puncture in the Parkinson's disease research participants: Parkinson's Progression Marker Initiative (PPMI)
Prakash N, Caspell-Garcia C, Coffey C, Siderowf A, Tanner C, Kieburtz K, Mollenhauer B, Galasko D, Merchant K, Foroud T, Chahine L, Weintraub D, Casaceli C, Dorsey R, Wilson R, Herzog M, Daegele N, Arnedo V, Frasier M, Sherer T, Marek K, Frank S, Jennings D, Simuni T, Marek K, Siderowf A, Seibyl J, Coffey C, Tanner C, Tosun-Turgut D, Simuni T, Shaw L, Trojanowski J, Singleton A, Kieburtz K, Toga A, Mollenhauer B, Galasko D, Poewe W, Foroud T, Poston K, Sherer T, Chowdhury S, Frasier M, Kopil C, Arnedo V, Marek K, Daegele N, Casaceli C, Dorsey R, Wilson R, Mahes S, Seibyl J, Salerno C, Coffey C, Caspell-Garcia C, Toga A, Crawford K, Foroud T, Casalin P, Malferrari G, Weisz M, Orr-Urtreger A, Trojanowski J, Shaw L, Singleton A, Foroud T, Foroud T, Montine T, Foroud T, Russell D, Tanner C, Simuni T, Dahodwala N, Mollenhauer B, Galasko D, Poewe W, Giladi N, Factor S, Hogarth P, Standaert D, Hauser R, Jankovic J, Saint-Hilaire M, Richard I, Shprecher D, Fernandez H, Brockmann K, Rosenthal L, Barone P, Espay A, Rowe D, Marder K, Santiago A, Bressman S, Hu S, Isaacson S, Corvol J, Martinez J, Tolosa E, Tai Y, Politis M, Smejdir D, Rees L, Williams K, Kausar F, Williams K, Richardson W, Willeke D, Peacock S, Heim B, Mirelman A, Sommerfeld B, Freed A, Wakeman K, Blair C, Guthrie S, Harrell L, Hunter C, Thomas C, James R, Zimmerman G, Brown V, Mule J, Hilt E, Ribb K, Ainscough S, Wethington M, Ranola M, Santana H, Moreno J, Raymond D, Speketer K, Carvajal L, Carvalho S, Croitoru I, Garrido A, Payne L, Viswanth V, Severt L, Facheris M, Soares H, Mintun M, Cedarbaum J, Taylor P, Biglan K, Vandenbroucke E, Sheikh Z, Bingol B, Fischer T, Sardi P, Forrat R, Reith A, Egebjerg J, Hillert G, Saba B, Min C, Umek R, Mather J, De Santi S, Post A, Boess F, Taylor K, Grachev I, Avbersek A, Muglia P, Merchant K, Tauscher J. Feasibility and safety of lumbar puncture in the Parkinson's disease research participants: Parkinson's Progression Marker Initiative (PPMI). Parkinsonism & Related Disorders 2019, 62: 201-209. PMID: 30738748, PMCID: PMC8978879, DOI: 10.1016/j.parkreldis.2018.12.025.Peer-Reviewed Original ResearchConceptsParkinson's Progression Markers InitiativeProgression Markers InitiativeAdverse eventsLumbar punctureParkinson's diseasePD participantsBaseline lumbar puncturePhone one weekSerial lumbar puncturesCommon adverse eventsRelated adverse eventsCerebrospinal fluid analysisEarly Parkinson's diseaseLow back painLongitudinal observation studyPPMI participantsUnderwent collectionBack painOverall incidenceDopaminergic deficiencyProgression biomarkersFemale genderSafety dataHealthy volunteersHigh incidence
2018
Finding useful biomarkers for Parkinson’s disease
Chen-Plotkin AS, Albin R, Alcalay R, Babcock D, Bajaj V, Bowman D, Buko A, Cedarbaum J, Chelsky D, Cookson MR, Dawson TM, Dewey R, Foroud T, Frasier M, German D, Gwinn K, Huang X, Kopil C, Kremer T, Lasch S, Marek K, Marto JA, Merchant K, Mollenhauer B, Naito A, Potashkin J, Reimer A, Rosenthal LS, Saunders-Pullman R, Scherzer CR, Sherer T, Singleton A, Sutherland M, Thiele I, van der Brug M, Van Keuren-Jensen K, Vaillancourt D, Walt D, West A, Zhang J. Finding useful biomarkers for Parkinson’s disease. Science Translational Medicine 2018, 10 PMID: 30111645, PMCID: PMC6097233, DOI: 10.1126/scitranslmed.aam6003.Peer-Reviewed Original Research
2015
Impact of the Alzheimer's Disease Neuroimaging Initiative, 2004 to 2014
Weiner MW, Veitch DP, Aisen PS, Beckett LA, Cairns NJ, Cedarbaum J, Donohue MC, Green RC, Harvey D, Jack CR, Jagust W, Morris JC, Petersen RC, Saykin AJ, Shaw L, Thompson PM, Toga AW, Trojanowski JQ, Initiative A. Impact of the Alzheimer's Disease Neuroimaging Initiative, 2004 to 2014. Alzheimer's & Dementia 2015, 11: 865-884. PMID: 26194320, PMCID: PMC4659407, DOI: 10.1016/j.jalz.2015.04.005.Peer-Reviewed Original ResearchConceptsAlzheimer's Disease Neuroimaging InitiativeClinical trialsDisease Neuroimaging InitiativeAlzheimer's diseaseAD clinical trialsSurrogate outcome measureAD risk factorsTraumatic brain injuryPost-traumatic stress disorderAD risk allelesMultiple sclerosisRisk factorsBrain injuryAD progressionOutcome measuresEffective treatmentParkinson's diseaseImaging ligandsMilitary populationStress disorderRisk allelesDiseaseMultiple centersBiomarkersStandardized biomarkers
2010
Seeing with new eyes: Finding a path to early intervention trials in Alzheimer's disease
Cedarbaum JM, Crans G, Grundman M. Seeing with new eyes: Finding a path to early intervention trials in Alzheimer's disease. The Journal Of Nutrition Health & Aging 2010, 14: 306-309. PMID: 20306002, DOI: 10.1007/s12603-010-0069-y.Peer-Reviewed Original ResearchConceptsMild cognitive impairmentAlzheimer's diseaseOutcome measuresClinical Dementia Rating SumClinical staging algorithmsPrimary outcome measureAD clinical trialsEarly intervention trialsComprehensive outcome measuresIdentification of MCIClinical courseIntervention trialsAD patientsClinical trialsDementia pathologyClinical characterizationCognitive impairmentEarly identificationDegenerative disordersNormal cognitionStaging algorithmDiseaseBiomarker informationBiomarker dataTrials
1990
General assay for phosphoproteins in cerebrospinal fluid: A candidate market for paraneoplastic cerebellar degeneration
Gandy S, Grebb J, Rosen N, Albert K, Devinsky O, Blumberg H, Anderson N, Cedarbaum J, Porter R, Sedvall G, Posner J, Greengard P. General assay for phosphoproteins in cerebrospinal fluid: A candidate market for paraneoplastic cerebellar degeneration. Annals Of Neurology 1990, 28: 829-833. PMID: 2285268, DOI: 10.1002/ana.410280616.Peer-Reviewed Original ResearchConceptsProtein kinase C substrate proteinProtein kinase substratesProtein phosphorylation systemsSubstrate proteinsKinase substratePhosphorylation systemBiochemical characterizationCell typesPhosphoproteinNeuronal cellsNeuronal diseasesNeuronal enrichmentGeneral assayUnique markerPotential insightsNeuronal populationsProteinNeurological diseasesCerebellar degenerationCellsAssaysEnrichmentAssay techniquesKdMarkers