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
2022
Application 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 modelProgressionSeverityPatientsDiseaseTrial of Cinpanemab in Early Parkinson’s Disease
Lang A, Siderowf A, Macklin E, Poewe W, Brooks D, Fernandez H, Rascol O, Giladi N, Stocchi F, Tanner C, Postuma R, Simon D, Tolosa E, Mollenhauer B, Cedarbaum J, Fraser K, Xiao J, Evans K, Graham D, Sapir I, Inra J, Hutchison R, Yang M, Fox T, Budd Haeberlein S, Dam T. Trial of Cinpanemab in Early Parkinson’s Disease. New England Journal Of Medicine 2022, 387: 408-420. PMID: 35921450, DOI: 10.1056/nejmoa2203395.Peer-Reviewed Original ResearchConceptsEarly Parkinson's diseasePrimary end pointSecondary end pointsWeek 52Parkinson's diseaseEnd pointControl groupUnified Parkinson's Disease Rating Scale (UPDRS) total scoreDisease pathogenesisHuman-derived monoclonal antibodiesΑ-synucleinCommon adverse eventsPhase 2 trialDisease-modifying treatmentsMDS-UPDRS scoresLack of efficacyDAT SPECT imagingAdjusted mean differenceMovement Disorder SocietyParkinson's disease pathogenesisScale total scoreAdverse eventsIntravenous infusionDAT-SPECTDisease progressionTracking Emergence of New Motor and Non-Motor Symptoms Using the MDS-UPDRS: A Novel Outcome Measure for Early Parkinson’s Disease?
Tosin M, Simuni T, Stebbins G, Cedarbaum J. Tracking Emergence of New Motor and Non-Motor Symptoms Using the MDS-UPDRS: A Novel Outcome Measure for Early Parkinson’s Disease? Journal Of Parkinson's Disease 2022, 12: 1345-1351. PMID: 35466955, PMCID: PMC9198734, DOI: 10.3233/jpd-223170.Peer-Reviewed Original ResearchConceptsEmergent symptomsDisease progressionOutcome measuresParkinson's disease clinical trialsNon-motor symptomsEarly Parkinson's diseaseDaily Living ScalePatient-reported experiencesClinical rating scalesNovel outcome measuresSymptomatic treatmentPD progressionClinical trialsMedian numberDaily livingLiving ScaleParkinson's diseaseSummary scoresMDS-UPDRSUseful markerRating ScaleSTX groupProgressionStxSymptoms
2021
Detecting 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
2019
Randomized 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 range
2018
Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson's disease models
Weihofen A, Liu Y, Arndt JW, Huy C, Quan C, Smith BA, Baeriswyl JL, Cavegn N, Senn L, Su L, Marsh G, Auluck P, Montrasio F, Nitsch RM, Hirst WD, Cedarbaum JM, Pepinsky R, Grimm J, Weinreb PH. Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson's disease models. Neurobiology Of Disease 2018, 124: 276-288. PMID: 30381260, DOI: 10.1016/j.nbd.2018.10.016.Peer-Reviewed Original ResearchConceptsΑ-Syn pathologyParkinson's diseaseΑ-synDisease progressionMouse modelPrevention of PDPhase 2 clinical trialPD mouse modelPD brain tissueDisease modelsDopamine transporter densityParkinson's disease modelΑ-synuclein antibodyPromising therapeutic approachDifferent mouse modelsHealthy elderly individualsΑ-syn fibrilsEpitope mapping studiesDopaminergic terminalsRecombinant α-synPreclinical dataClinical trialsTherapeutic approachesMotor impairmentElderly individualsEffect of PD medication on disease progression as measured by rate of change in MDS_UPDRS in PPMI study (P2.042)
Xiao Z, Cedarbaum J, Yang M. Effect of PD medication on disease progression as measured by rate of change in MDS_UPDRS in PPMI study (P2.042). Neurology 2018, 90 DOI: 10.1212/wnl.90.15_supplement.p2.042.Peer-Reviewed Original Research
1994
Arrest of Motor Neuron Disease in wobbler Mice Cotreated with CNTF and BDNF
Mitsumoto H, Ikeda K, Klinkosz B, Cedarbaum J, Wong V, Lindsay R. Arrest of Motor Neuron Disease in wobbler Mice Cotreated with CNTF and BDNF. Science 1994, 265: 1107-1110. PMID: 8066451, DOI: 10.1126/science.8066451.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorCiliary neurotrophic factorMotor neuron diseaseNeurotrophic factorNeuron diseaseWobbler miceMotor neuron dysfunctionNeuron dysfunctionDisease progressionSubcutaneous injectionMotor neuronsHistological criteriaAnimal modeAnimal modelsAlternate daysSignaling pathwaysDiseaseMiceCellular signaling pathwaysProgressionDysfunctionFactorsCotreatmentNeuronsAdministrationThe effects of ciliary neurotrophic factor on motor dysfunction in wobbler mouse motor neuron disease
Mitsumoto H, Ikeda K, Holmlund T, Greene T, Cedarbaum J, Wong V, Lindsay R. The effects of ciliary neurotrophic factor on motor dysfunction in wobbler mouse motor neuron disease. Annals Of Neurology 1994, 36: 142-148. PMID: 8053649, DOI: 10.1002/ana.410360205.Peer-Reviewed Original ResearchConceptsCiliary neurotrophic factorNeurotrophic factorMotor neuron diseaseHuman ciliary neurotrophic factorGrip strengthNeuron diseaseBody weightWobbler mouse motor neuron diseaseMotor neuron disease modelMouse motor neuron diseaseFirst neurotrophic factorMean grip strengthImproved muscle strengthVehicle-treated animalsWeeks of treatmentMuscle twitch tensionSurvival-promoting effectsWobbler mouse modelRat ciliary neurotrophic factorMotor dysfunctionControl miceMuscle strengthDisease progressionMotor neuronsTwitch tension