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
Trial 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 progression
2021
Systematic 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 ResearchMeSH KeywordsAlpha-SynucleinAmyotrophic Lateral SclerosisBiomarkersFrontotemporal DementiaHumansMultiple System AtrophyTau ProteinsConceptsGlial 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 chain
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 rangeA 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
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 ResearchMeSH KeywordsAlpha-SynucleinAnimalsAntibodies, MonoclonalHumansMiceParkinsonian DisordersPhenotypeProtein AggregatesConceptsΑ-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 individualsTargeted 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 ResearchMeSH KeywordsAlpha-SynucleinAnimalsClinical Trials as TopicGlucosylceramidaseHumansParkinson DiseaseProtein Serine-Threonine KinasesConceptsParkinson's diseaseGreat unmet medical needDisease-modifying treatmentsNew therapeutic approachesUnmet medical needClinical stageClinical trialsRelentless progressionTherapeutic approachesPotential therapyClinical developmentTherapeutic paradigmMedical needDiseaseGenetic variantsPD geneticsNew arsenalTreatmentGenetic discoveriesKey outstanding questionsTherapySymptomsPathologyProgressionTrials