2023
Relative Meaningfulness and Impacts of Symptoms in People with Early-Stage Parkinson’s Disease
Mammen J, Speck R, Stebbins G, Müller M, Yang P, Campbell M, Cosman J, Crawford J, Dam T, Hellsten J, Jensen-Roberts S, Kostrzebski M, Simuni T, Barowicz K, Cedarbaum J, Dorsey E, Stephenson D, Adams J. Relative Meaningfulness and Impacts of Symptoms in People with Early-Stage Parkinson’s Disease. Journal Of Parkinson's Disease 2023, 13: 619-632. PMID: 37212071, PMCID: PMC10357209, DOI: 10.3233/jpd-225068.Peer-Reviewed Original ResearchConceptsEarly Parkinson's diseaseMeaningful symptomsParkinson's diseaseEarly-stage Parkinson's diseaseMost bothersome symptomsImpact of symptomsStage Parkinson's diseaseBothersomeness of symptomsFine motor difficultiesBothersome symptomsImpact of diseasePatient's perspectiveImportant symptomNew therapiesFuture symptomsSymptom mappingSymptomsMotor difficultiesDiseaseExperiences of peopleJob functioningThe Influence of GBA and LRRK2 on Mood Disorders in Parkinson's Disease
DeBroff J, Omer N, Cohen B, Giladi N, Kestenbaum M, Shirvan J, Cedarbaum J, Gana‐Weisz M, Goldstein O, Orr‐Urtreger A, Mirelman A, Thaler A. The Influence of GBA and LRRK2 on Mood Disorders in Parkinson's Disease. Movement Disorders Clinical Practice 2023, 10: 606-616. PMID: 37070047, PMCID: PMC10105114, DOI: 10.1002/mdc3.13722.Peer-Reviewed Original ResearchDiagnosis of PDParkinson's diseaseMood-related disordersTime of assessmentMood disordersIdiopathic PDNon-motor comorbiditiesNon-motor featuresIdiopathic Parkinson's diseaseNon-motor phenotypeFrequency of depressionMood related disordersState of depressionPD patientsSuch medicationsWorse motorGenetic statusMedicationsProdromal stageRelated disordersGBA genePD diagnosisDiseaseDiagnosisDisorders
2022
Neuromelanin and T2*-MRI for the assessment of genetically at-risk, prodromal, and symptomatic Parkinson’s disease
Ben Bashat D, Thaler A, Lerman Shacham H, Even-Sapir E, Hutchison M, Evans K, Orr-Urterger A, Cedarbaum J, Droby A, Giladi N, Mirelman A, Artzi M. Neuromelanin and T2*-MRI for the assessment of genetically at-risk, prodromal, and symptomatic Parkinson’s disease. Npj Parkinson's Disease 2022, 8: 139. PMID: 36271084, PMCID: PMC9586960, DOI: 10.1038/s41531-022-00405-9.Peer-Reviewed Original ResearchParkinson's diseaseGenotype-related differencesDAT-SPECTRadiomic featuresSymptomatic Parkinson's diseaseSignificant correlationProdromal phaseBrain regionsNeuromelanin MRIIron accumulationDiseaseMRIAssessment of individualsImaging valuesRadiomics analysisSignificant differencesPatientsNeuromelaninRiskAgeScoresT2Ratio scoresGroupLR scoresApplication of longitudinal item response theory models to modeling Parkinson’s disease progression
Zou H, Aggarwal V, Stebbins G, Müller M, Cedarbaum J, Pedata A, Stephenson D, Simuni T, Luo S. Application of longitudinal item response theory models to modeling Parkinson’s disease progression. CPT Pharmacometrics & Systems Pharmacology 2022, 11: 1382-1392. PMID: 35895005, PMCID: PMC9574723, DOI: 10.1002/psp4.12853.Peer-Reviewed Original ResearchConceptsEarly Parkinson's diseaseParkinson's diseaseDisease progressionProgression rateUnified Parkinson's Disease Rating Scale part 2Stage 1Yahr stage 1Higher baseline severityCommon clinical outcomeLongitudinal disease progressionSlow progression rateParkinson's disease progressionMovement Disorder SocietyStage 2Clinical outcomesMotor signsBaseline severitySlow progressionSum scoreTotal scoreLongitudinal item response theory modelProgressionSeverityPatientsDisease
2021
Glucocerebrosidase Activity is not Associated with Parkinson's Disease Risk or Severity
Omer N, Giladi N, Gurevich T, Bar‐Shira A, Gana‐Weisz M, Glinka T, Goldstein O, Kestenbaum M, Cedarbaum J, Mabrouk O, Fraser K, Shirvan J, Orr‐Urtreger A, Mirelman A, Thaler A. Glucocerebrosidase Activity is not Associated with Parkinson's Disease Risk or Severity. Movement Disorders 2021, 37: 190-195. PMID: 34550621, PMCID: PMC9292990, DOI: 10.1002/mds.28792.Peer-Reviewed Original ResearchConceptsNon-manifesting carriersProdromal Parkinson's diseaseParkinson's diseaseGCase activityClinical phenotypeLower GCase activityCarriers of mutationsLysosomal enzyme glucocerebrosidaseGBA-NMCGBA-PDPD patientsRisk factorsGBA mutationsPD phenotypeG2019S LRRK2GBA geneEnzyme glucocerebrosidaseLRRK2 genePerformance-based measuresAshkenazi JewsDiseaseGroups of participantsPhenotypeMutationsParticipantsSeeking 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 successTherapyStrokeBiomarkersDetecting Sensitive Mobility Features for Parkinson's Disease Stages Via Machine Learning
Mirelman A, Frank M, Melamed M, Granovsky L, Nieuwboer A, Rochester L, Del Din S, Avanzino L, Pelosin E, Bloem B, Della Croce U, Cereatti A, Bonato P, Camicioli R, Ellis T, Hamilton J, Hass C, Almeida Q, Inbal M, Thaler A, Shirvan J, Cedarbaum J, Giladi N, Hausdorff J. Detecting Sensitive Mobility Features for Parkinson's Disease Stages Via Machine Learning. Movement Disorders 2021, 36: 2144-2155. PMID: 33955603, DOI: 10.1002/mds.28631.Peer-Reviewed Original ResearchConceptsParkinson's diseaseDisease stageMid-stage Parkinson's diseaseAge-matched healthy controlsEarly Parkinson's diseaseHigh discriminatory valueBilateral anklesDisease progressionClinical trialsHealthy controlsDisease spectrumGait measuresSeverity stagesAdvanced stageTrunk sensorDisease severityStride timingStudy participantsDiscriminatory valueObjective monitoringMobility measuresDiseaseCohort selectionMean sensitivity
2020
Metabolic syndrome does not influence the phenotype of LRRK2 and GBA related Parkinson’s disease
Thaler A, Shenhar-Tsarfaty S, Shaked Y, Gurevich T, Omer N, Bar-Shira A, Gana-Weisz M, Goldstein O, Kestenbaum M, Cedarbaum JM, Orr-Urtreger A, Giladi N, Mirelman A. Metabolic syndrome does not influence the phenotype of LRRK2 and GBA related Parkinson’s disease. Scientific Reports 2020, 10: 9329. PMID: 32518334, PMCID: PMC7283235, DOI: 10.1038/s41598-020-66319-9.Peer-Reviewed Original ResearchConceptsMetabolic syndromeParkinson's diseaseLRRK2-NMCLRRK2-PDComponents of MSGBA-Parkinson diseaseMetabolic componentsProdromal Parkinson's diseaseHigh triglyceride levelsIdiopathic Parkinson's diseaseGBA-NMCGBA-PDElevated triglyceridesBlood pressureLRRK2 carriersProdromal featuresTriglyceride levelsPD groupDiseaseDisease statesLaboratory test resultsPrediabetesSyndromeHigh rateTriglyceridesA Possible Modifying Effect of the G2019S Mutation in the LRRK2 Gene on GBA Parkinson's Disease
Omer N, Giladi N, Gurevich T, Bar‐Shira A, Gana‐Weisz M, Goldstein O, Kestenbaum M, Cedarbaum JM, Orr‐Urtreger A, Mirelman A, Thaler A. A Possible Modifying Effect of the G2019S Mutation in the LRRK2 Gene on GBA Parkinson's Disease. Movement Disorders 2020, 35: 1249-1253. PMID: 32353202, DOI: 10.1002/mds.28066.Peer-Reviewed Original ResearchConceptsGBA-PDLRRK2-PDIdiopathic Parkinson's diseaseDisease Rating ScaleParkinson's diseaseTotal Unified Parkinson's Disease Rating ScaleUnified Parkinson's Disease Rating ScaleParkinson's Disease Rating ScaleG2019S LRRK2 mutationBetter olfactionClinical symptomsPatientsGBA genePhenotypic presentationRating ScalePerformance-based measuresPhenotypic expressionDiseaseLower scoresPresentationMutationsSymptomsBaseline Characteristics of Participants of the SPARK Trial, a Phase 2 Study of the anti-alpha-synuclein antibody Cinpanemab (BIIB054) in Parkinson’s Disease (1579)
Fox T, Siderowf A, Fernandez H, Tanner C, Postuma R, Simon D, Byrne M, Lang A, Brooks D, Rascol O, Tolosa E, Poewe W, Stocchi F, Mollenhauer B, Giladi N, Hirschhorn B, Cedarbaum J, Nomikos G, Fanning L, Yang M, Xiao J, Brys M. Baseline Characteristics of Participants of the SPARK Trial, a Phase 2 Study of the anti-alpha-synuclein antibody Cinpanemab (BIIB054) in Parkinson’s Disease (1579). Neurology 2020, 94 DOI: 10.1212/wnl.94.15_supplement.1579.Peer-Reviewed Original ResearchDisease 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 researchTossing and Turning in Bed: Nocturnal Movements in Parkinson's Disease
Mirelman A, Hillel I, Rochester L, Del Din S, Bloem BR, Avanzino L, Nieuwboer A, Maidan I, Herman T, Thaler A, Gurevich T, Kestenbaum M, Orr‐Urtreger A, Brys M, Cedarbaum JM, Giladi N, Hausdorff JM. Tossing and Turning in Bed: Nocturnal Movements in Parkinson's Disease. Movement Disorders 2020, 35: 959-968. PMID: 32080891, DOI: 10.1002/mds.28006.Peer-Reviewed Original ResearchConceptsAdvanced Parkinson's diseaseParkinson's diseaseNocturnal hypokinesiaDopaminergic medicationSleep disturbancesDisease severityDiverse disease severitiesPD motor severityUpright periodsDopaminergic treatmentNonmotor symptomsUpright timeMotor severityHealthy controlsSleep interruptionDisease spectrumPatientsSeverityMedicationsHypokinesiaDiseaseNocturnal movementsDegree of rotationTri-axial accelerometerDysautonomia
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: 825-825. PMID: 31524182, PMCID: PMC6878913, DOI: 10.3233/jpd-199003.Peer-Reviewed Original ResearchRandomized phase I clinical trial of anti–α‐synuclein antibody BIIB054
Brys M, Fanning L, Hung S, Ellenbogen A, Penner N, Yang M, Welch M, Koenig E, David E, Fox T, Makh S, Aldred J, Goodman I, Pepinsky B, Liu Y, Graham D, Weihofen A, Cedarbaum JM. Randomized phase I clinical trial of anti–α‐synuclein antibody BIIB054. Movement Disorders 2019, 34: 1154-1163. PMID: 31211448, PMCID: PMC6771554, DOI: 10.1002/mds.27738.Peer-Reviewed Original ResearchConceptsParkinson's disease participantsΑ-synucleinHealthy volunteersParkinson's diseaseHuman-derived monoclonal antibodiesSingle-dose cohortsMost adverse eventsFurther clinical developmentImmunotherapy targetingStudy drugAdverse eventsFavorable safetySingle doseNeuronal dysfunctionSerum ratioDisease progressionCerebrospinal fluidClinical developmentPharmacokinetic parametersPharmacokinetic profileSerum exposureLaboratory assessmentMonoclonal antibodiesDiseaseDose rangeMolecular 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 strides
2018
Targeted Therapies for Parkinson's Disease: From Genetics to the Clinic
Sardi SP, Cedarbaum JM, Brundin P. Targeted Therapies for Parkinson's Disease: From Genetics to the Clinic. Movement Disorders 2018, 33: 684-696. PMID: 29704272, PMCID: PMC6282975, DOI: 10.1002/mds.27414.Peer-Reviewed Original ResearchConceptsParkinson's diseaseGreat unmet medical needDisease-modifying treatmentsNew therapeutic approachesUnmet medical needClinical stageClinical trialsRelentless progressionTherapeutic approachesPotential therapyClinical developmentTherapeutic paradigmMedical needDiseaseGenetic variantsPD geneticsNew arsenalTreatmentGenetic discoveriesKey outstanding questionsTherapySymptomsPathologyProgressionTrialsRandomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study of Anti-Alpha-Synuclein Antibody BIIB054 in Patients with Parkinson’s Disease (S26.001)
Brys M, Ellenbogen A, Fanning L, Penner N, Yang M, Welch M, Koenig E, David E, Fox T, Makh S, Aldred J, Goodman I, Graham D, Weihofen A, Cedarbaum J. Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study of Anti-Alpha-Synuclein Antibody BIIB054 in Patients with Parkinson’s Disease (S26.001). Neurology 2018, 90 DOI: 10.1212/wnl.90.15_supplement.s26.001.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
2013
P1–343: A phase II study of the gamma‐secretase inhibitor avagacestat (BMS‐708163) in predementia Alzheimer's disease
Coric V, Salloway S, van Dyck C, Kerselaers W, Kaplita S, Curtis C, Ross J, Richter R, Andreasen N, Brody M, Sharma S, Cedarbaum J, Berman R. P1–343: A phase II study of the gamma‐secretase inhibitor avagacestat (BMS‐708163) in predementia Alzheimer's disease. Alzheimer's & Dementia 2013, 9: p283-p283. DOI: 10.1016/j.jalz.2013.05.569.Peer-Reviewed Original Research