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 ResearchMeSH KeywordsAlpha-SynucleinAntibodies, MonoclonalAntiparkinson AgentsBiomarkersDisease ProgressionDopamineDouble-Blind MethodHumansParkinson DiseaseConceptsDisease 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
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 ResearchMeSH KeywordsAdultAgedAlpha-SynucleinAntibodies, MonoclonalDouble-Blind MethodFemaleHumansImmunologic FactorsMaleMiddle AgedParkinson DiseaseConceptsParkinson'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
2011
A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease
Salloway S, Sperling R, Keren R, Porsteinsson AP, van Dyck CH, Tariot PN, Gilman S, Arnold D, Abushakra S, Hernandez C, Crans G, Liang E, Quinn G, Bairu M, Pastrak A, Cedarbaum JM. A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease. Neurology 2011, 77: 1253-1262. PMID: 21917766, PMCID: PMC3179648, DOI: 10.1212/wnl.0b013e3182309fa5.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesApolipoprotein E4Dose-Response Relationship, DrugDouble-Blind MethodFemaleFollow-Up StudiesHumansInositolMagnetic Resonance ImagingMaleMental Status ScheduleMiddle AgedPeptide FragmentsPlatelet Aggregation InhibitorsTime FactorsTreatment OutcomeConceptsNeuropsychological test batteryAlzheimer's diseaseDose-ranging phase 2 studyAlzheimer's Disease Cooperative Study-ActivitiesClass II trialsClinical efficacy outcomesCSF biomarker resultsScyllo-inositol concentrationsPhase 2 studyPrimary efficacy analysisHigh-dose groupDaily Living ScaleBrain ventricular volumeCoprimary endpointsEarly discontinuationEfficacy outcomesII trialADCS-ADLDose groupEfficacy analysisAcceptable safetyAβx-42Living ScaleOptimal doseTreatment groups
2005
NT-3 promotes nerve regeneration and sensory improvement in CMT1A mouse models and in patients
Sahenk Z, Nagaraja HN, McCracken BS, King WM, Freimer ML, Cedarbaum JM, Mendell JR. NT-3 promotes nerve regeneration and sensory improvement in CMT1A mouse models and in patients. Neurology 2005, 65: 681-689. PMID: 16157899, DOI: 10.1212/01.wnl.0000171978.70849.c5.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnimalsCharcot-Marie-Tooth DiseaseDisease Models, AnimalDouble-Blind MethodFemaleHumansMaleMiceMice, Neurologic MutantsMice, NudeMice, TransgenicMiddle AgedMyelin ProteinsNerve RegenerationNeurotrophin 3Pilot ProjectsRecovery of FunctionSciatic NeuropathySural NerveTransplantation, HeterologousTreatment OutcomeConceptsNeuropathy Impairment ScoreNT-3 groupNT-3 treatmentNeurotrophin-3Placebo groupAnimal modelsNerve regenerationNude mice axonsQuantitative muscle testingSural nerve biopsyPrimary outcome measurePeripheral myelin proteinPilot clinical studyTooth type 1ANerve biopsyMuscle testingAxonal regenerationClinical studiesImpairment scoresOutcome measuresPreclinical studiesMouse modelEndpoint measuresElectrophysiologic measurementsNude mice
2003
Neurotrophin-3 Improves Functional Constipation
Parkman HP, Rao SS, Reynolds JC, Schiller LR, Wald A, Miner PB, Lembo AJ, Gordon JM, Drossman DA, Waltzman L, Stambler N, Cedarbaum JM. Neurotrophin-3 Improves Functional Constipation. The American Journal Of Gastroenterology 2003, 98: ajg2003312. PMID: 12818279, DOI: 10.1111/j.1572-0241.2003.t01-1-07477.x.Peer-Reviewed Original ResearchConceptsComplete bowel movementsNeurotrophin-3Bowel movementsColon transitFunctional constipationChronic constipationStool frequencyPlacebo-controlled phase II studyTransient injection site reactionsConstipation-related symptomsFrequent adverse eventsPhase II studyThird of patientsInjection site reactionsEnd of treatmentDose-related effectsConstipated subjectsBowel functionPrimary endpointAdverse eventsII studyImproved symptomsWeekly dosingNeurotrophic factorConstipation
1997
Performance of the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) in multicenter clinical trials
Cedarbaum J, Stambler N. Performance of the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) in multicenter clinical trials. Journal Of The Neurological Sciences 1997, 152: s1-s9. PMID: 9419047, DOI: 10.1016/s0022-510x(97)00237-2.Peer-Reviewed Original ResearchConceptsAmyotrophic Lateral Sclerosis Functional Rating ScaleFunctional Rating ScaleMulticenter clinical trialFunctional statusRating ScaleClinical trialsPatients' functional statusClinical Global ImpressionMuscle strength testingArea of feedingPlacebo patientsTherapeutic trialsTest-retest reliabilityGlobal ImpressionPatient levelTreatment studiesChange ScaleTrialsPatientsMaximum scoreIndependent assessmentStrength testingAmbulation
1991
Effect of MK-458 (HPMC) in Parkinson's Disease Previously Untreated With Dopaminergic Drugs. A Double-Blind, Placebo-Controlled Multicenter Study.
Koller WC, Block GA, Ahlskog JE, Ahrens S, Cedarbaum JM, Cyhan G, Goetz CG, LeWitt PA, Liss C, McLean L, Moses H, Muenter M, Nausieda P, Sanchez-Ramos J, Reich S, Singer C, Stellar S, Weiner W. Effect of MK-458 (HPMC) in Parkinson's Disease Previously Untreated With Dopaminergic Drugs. A Double-Blind, Placebo-Controlled Multicenter Study. Clinical Neuropharmacology 1991, 14: 322. PMID: 1913699, DOI: 10.1097/00002826-199108000-00004.Peer-Reviewed Original ResearchMeSH KeywordsAgedDelayed-Action PreparationsDouble-Blind MethodFemaleHumansLactoseMaleMethylcelluloseMiddle AgedOxazinesParkinson DiseaseConceptsMK-458Early Parkinson's diseaseParkinson's diseaseDopaminergic drugsDisability Rating ScoreDopamine receptor agonismPlacebo-controlled evaluationPatient global assessmentClinical rating scalesParkinsonian symptomsAntiparkinsonian efficacyMulticenter studyAdverse reactionsIdeal treatmentReceptor agonistReceptor agonismSustained release formulationPlaceboGlobal assessmentDiseaseRating ScaleSignificant decreaseDrugsPatientsRating scores
1990
Results of long-term treatment with controlled-release levodopa/carbidopa (Sinemet CR)
Cedarbaum JM, Silvestri M, Clark M, Toy L, Harts A, Green-Parsons A, McDowell FH. Results of long-term treatment with controlled-release levodopa/carbidopa (Sinemet CR). Journal Of Neural Transmission: Parkinson's Disease A And Dementia Section 1990, 2: 205-213. PMID: 2257060, DOI: 10.1007/bf02257651.Peer-Reviewed Original ResearchConceptsStandard SinemetMotor response fluctuationsResponse fluctuationsSinemet CRDisease patientsControlled-release levodopa/carbidopaLevodopa/carbidopaLong-term treatmentParkinson's disease patientsLong-term managementAntiparkinson effectEligible patientsMost patientsMedication dosesInterdose intervalClinical trialsParkinson's diseaseUseful adjunctPatientsSinemetDiseaseYearsCarbidopaAdjunctDose
1989
A double-blind crossover comparison of Sinemet CR4 and standard Sinemet 25/100 in patients with Parkinson's disease and fluctuating motor performance.
Cedarbaum JM, Hoey M, McDowell FH. A double-blind crossover comparison of Sinemet CR4 and standard Sinemet 25/100 in patients with Parkinson's disease and fluctuating motor performance. Journal Of Neurology Neurosurgery & Psychiatry 1989, 52: 207. PMID: 2649640, PMCID: PMC1032507, DOI: 10.1136/jnnp.52.2.207.Peer-Reviewed Original ResearchConceptsStandard Sinemet 25/100Sinemet 25/100Sinemet CR4Controlled-release levodopa/carbidopaDouble-blind crossover comparisonDaily medication dosesDouble-blind partMean interdose intervalLevodopa/carbidopaAntiparkinson effectMedication dosesInterdose intervalSevere dyskinesiaCrossover comparisonCrossover trialParkinsonian patientsTherapeutic responseMedication administrationMotor functionAntiparkinsonian agentsParkinson's diseaseOpen treatmentMotor responsePatientsMotor performance