2024
Quantification of Cinpanemab (BIIB054) Binding to α-Synuclein in Cerebrospinal Fluid of Phase 1 Single Ascending Dose Samples
Liu Y, Yang M, Fraser K, Graham D, Weinreb P, Weihofen A, Hirst W, Cedarbaum J, Pepinsky B. Quantification of Cinpanemab (BIIB054) Binding to α-Synuclein in Cerebrospinal Fluid of Phase 1 Single Ascending Dose Samples. Journal Of Pharmacology And Experimental Therapeutics 2024, jpet-ar-2024-002199. PMID: 38936981, DOI: 10.1124/jpet.124.002199.Peer-Reviewed Original ResearchCentral nervous systemCerebrospinal fluidMeso Scale DiscoveryCentral nervous system compartmentDrug concentrationsA-synCerebrospinal fluid samplesParkinson's diseasePassive immunotherapy approachesSite of actionImmunotherapy approachesLow drug concentrationsImmunotherapy trialsHealthy volunteersSystemic compartmentDrug-target interactionsCSF samplesObserved doseNervous systemTherapeutic targetA-syn levelsClinical samplesTime-dependent bindingComplex formationCross-linking method
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 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 blood
2020
Low cerebrospinal fluid volume and the risk for post-lumbar puncture headaches
Droby A, Omer N, Gurevich T, Kestenbaum M, Mina Y, Cedarbaum JM, Aizenstein O, Giladi N, Mirelman A, Thaler A. Low cerebrospinal fluid volume and the risk for post-lumbar puncture headaches. Journal Of The Neurological Sciences 2020, 417: 117059. PMID: 32739500, DOI: 10.1016/j.jns.2020.117059.Peer-Reviewed Original ResearchConceptsPost-LP headachePost-lumbar puncture headacheLow CSF volumeT1-weighted imagesCerebrospinal fluidCSF volumePuncture headacheDisease-modifying clinical trialsLow cerebrospinal fluid (CSF) volumePatient-related factorsGradient-echo T1-weighted imagesCerebrospinal fluid volumeLP headacheAdverse eventsMedical workupClinical trialsBrain MRINeurological conditionsHeadacheMRI scansT MR scannerWhite matterCSF collectionGray matterPilot study
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
2013
Pharmacokinetic Profile of Orally Administered Scyllo‐Inositol (Elnd005) in Plasma, Cerebrospinal Fluid and Brain, and Corresponding Effect on Amyloid‐Beta in Healthy Subjects
Liang E, Garzone P, Cedarbaum JM, Koller M, Tran T, Xu V, Ross B, Jhee SS, Ereshefsky L, Pastrak A, Abushakra S. Pharmacokinetic Profile of Orally Administered Scyllo‐Inositol (Elnd005) in Plasma, Cerebrospinal Fluid and Brain, and Corresponding Effect on Amyloid‐Beta in Healthy Subjects. Clinical Pharmacology In Drug Development 2013, 2: 186-194. PMID: 27121673, DOI: 10.1002/cpdd.14.Peer-Reviewed Original ResearchAverage trough concentrationCerebrospinal fluidAlzheimer's diseaseTrough concentrationsDay 8Magnetic resonance spectroscopy scansCSF drug levelsHealthy young subjectsPredetermined time pointsOral treatmentCSF levelsAmyloid-beta fragmentsCSF concentrationsPlasma levelsDrug levelsHealthy subjectsAmyloid betaCSF samplesPharmacokinetic profileYoung subjectsTransgenic modelBaseline levelsTime pointsWhite matter voxelsAβ fragments
2011
P2‐509: Population pharmacokinetic analysis of plasma, cerebrospinal fluid and brain ELND005 in patients with mild to moderate Alzheimer's disease
Wagg J, Green M, Yan L, Liang E, Cedarbaum J, Abushakra S. P2‐509: Population pharmacokinetic analysis of plasma, cerebrospinal fluid and brain ELND005 in patients with mild to moderate Alzheimer's disease. Alzheimer's & Dementia 2011, 7: s475-s475. DOI: 10.1016/j.jalz.2011.05.1380.Peer-Reviewed Original Research
1991
Dopamine sulfate in ventricular cerebrospinal fluid and motor function in Parkinson's disease.
Cedarbaum J, Olanow CW. Dopamine sulfate in ventricular cerebrospinal fluid and motor function in Parkinson's disease. Neurology 1991, 41: 1567-70. PMID: 1922797, DOI: 10.1212/wnl.41.10.1567.Peer-Reviewed Original ResearchConceptsAdvanced Parkinson's diseaseDopamine sulfateParkinson's diseaseDopamine sulfate levelsLevodopa/carbidopaTime of transplantationPeak plasma concentrationAvailability of dopamineVentricular cerebrospinal fluidSulfate levelsClinical improvementMotor fluctuationsOmmaya reservoirSingle doseExogenous levodopaParkinsonian brainMotor functionPlasma concentrationsLateral ventricleCerebrospinal fluidAdrenal medullaLevodopaPatientsDiseaseDopamineTemporal relationships between plasma and cerebrospinal fluid pharmacokinetics of levodopa and clinical effect in Parkinson's disease
Olanow CW, Gauger LL, Cedarbaum JM. Temporal relationships between plasma and cerebrospinal fluid pharmacokinetics of levodopa and clinical effect in Parkinson's disease. Annals Of Neurology 1991, 29: 556-559. PMID: 1859185, DOI: 10.1002/ana.410290516.Peer-Reviewed Original ResearchConceptsVentricular cerebrospinal fluidCerebrospinal fluidParkinson's diseasePlasma levodopa concentrationsAdvanced Parkinson's diseaseCerebrospinal fluid pharmacokineticsPharmacokinetics of levodopaCentral nervous systemLevodopa levelsOmmaya reservoirClinical effectsLevodopa effectsParkinsonian patientsLevodopa concentrationsHomovanillic acidNervous systemDrug concentrationsLevodopaDiseaseMotor performancePatientsTime coursePharmacokineticsTemporal relationshipNucleus transplantation