Jesse M. Cedarbaum, MD, FAAN (Neurology), FANA
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Medical School Recruit - Professor
Biography
A 1978 YSM graduate, I am a neurologist/clinical trialist with sub-specialty in Movement Disorders. After 7 years heading the Parkinson and Movement Disorders program at New York-Hospital Cornell, I have spent the majority of his career as an executive in the pharmaceutical industry, leading teams in the areas of neurodegenerative, neuropsychiatric and retinal disorders at Regeneron, Elan, Cytokinetics and Bristol-Myers Squibb. Most recently I led a team at Biogen that advanced 3 new compounds into the clinic for potential treatment of Parkinson’s disease. At Biogen I also established a clinical research program in inherited ataxias. My research activities have encompassed efforts to develop novel clinical outcome measures and biomarkers, including digital health technologies for clinical trials. I have served as chair of the ADNI Private Partner Scientific Board, the Industry Scientific Advisory Board of the Michael J. Fox Foundation-sponsored Parkinson Progression Markers Initiative, and as industry co-chair of the Critical Path for Parkinson’s consortium. I have authored or-co-authored over 100 papers and book chapters, mostly in the area of neurological and opthalmological therapeutics , especially therapeutic development for Movement Disorders
Appointments
Education & Training
- Resident
- New York Hospital-Cornell Medical Center (1983)
- Intern and Resident
- University of Chicago Hospitals and Clinics (1980)
- MD
- Yale University School of Medicine (1978)
- MA
- Stanford University, Biology
- AB
- Stanford University, Human Biology
Board Certifications
Neurology
- Certification Organization
- AB of Psychiatry & Neurology
- Original Certification Date
- 1985
Research
Overview
The early focus of my work was on using neuroanatomical and neurophysiological tools to understand the pharmacology of drugs acting on the noradrenergic system of the brain, and the contribution of the locus coeruleus (LC) noradrenergic system to brain function. These efforts helped lay the groundwork for a theory of locus coeruleus function that is still widely supported – that the LC is involved in novelty detection and selective attention. Subsequent understanding of pathological changes in the LC and the correlation of loss of noradrenergic function in dementia are in keeping with this hypothesis.
My interest in the pharmacology of catecholaminergic systems in the brain led to a clinical interest in Parkinson’s disease. Significant novel clinical observations from work carried out at Cornell and the Burke Rehabilitation Center included the (at that time) novel understanding that the timing emergence of MRF and dyskinesia in the treatment of PD was related to age of onset and severity of disease, not the duration of levodopa administration. In addition, our group was among the first to report on the near-universal prevalence of dementia in advanced PD. Our group also was among the early pioneers in the utilization of enteral levodopa infusions to attempt to control MRFs, and we established the basis for the use of peripheral COMT inhibitors in PD through a combination of clinical observations and studies using novel COMT inhibitors in nonhuman primates. And finally, we described the relationship between plasma and brain pharmacokinetics levodopa and dopamine by sampling CSF from PD patients who had Ommaya reservoirs left in place following neurosurgical procedures.
Prior to initiation of clinical trials for ALS at Regeneron Pharmaceuticals, it became apparent to us that there was a need for a comprehensive clinical rating scale to be used as a clinical trial outcome measure. This work resulted in the development and validation of the ALS Functional Rating Scale (ALSFRS) and its revised, expanded version, the ALSFRS-R. Unfortunately, none of our ALS clinical trials were successful, but the ALSFRS-R continues to be the most-used outcome measure for ALS trials, and is endorsed by FDA for this use.
The neurotrophic factor trail led us to studies for treatment of retinal disorders, since the eye, after all, is a part of, and a window into, the brain. Subsequent to the completion of the ALS program, I led a series of clinical trials of an anti-VEGF agent, aflibercept, for treatment of neovascular Age Related Macular Degeneration (“wet”) AMD. This program resulted in the eventual approval of the drug, known commercially as Eyelea, for wet AMD and a variety of other retinal vascular diseases.
After leaving Regeneron, I joined Elan Pharmaceuticals. There my focus shifted back to neurodegenerative disease, in particular Alzheimer’s disease. Three publications from this period helped lay the groundwork for acceptance by both FDA and EMA of the Clinical Dementia Rating Sum of Boxes (CDR-SB), developed at Washington University in St. Louis, as a sole clinical outcome measure for trials in the MCI-early AD space, and its adoption as the outcome measure for most contemporary MCI-mild AD clinical trials.
Most recently, as we prepared for the development of novel therapeutic agents for the treatment of PD at Biogen, I established a number of external collaborative projects that resulted in the identification and preliminary validation of novel or pre-existing biomarkers for PD clinical trials, and helped lead pre-competitive collaborative efforts to secure regulatory support for the use of dopamine transporter (DaT) imaging as an enrichment biomarker for PD clinical trials.
Medical Research Interests
Public Health Interests
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Christopher van Dyck, MD
Hilary Blumberg, MD
Scott Gettinger, MD
Vladimir Coric, MD
Parkinson Disease
Motor Neuron Disease
Multiple System Atrophy
Cerebellar Ataxia
Publications
2024
Validating new symptom emergence as a patient-centric outcome measure for PD clinical trials
Zou H, Stebbins G, Simuni T, Luo S, Cedarbaum J. Validating new symptom emergence as a patient-centric outcome measure for PD clinical trials. Parkinsonism & Related Disorders 2024, 128: 107118. PMID: 39353265, DOI: 10.1016/j.parkreldis.2024.107118.Peer-Reviewed Original ResearchAltmetricConceptsPD clinical trialsClinical trialsEmergent symptomsPhase 3 clinical trialsPhase 3 studySlowing of disease progressionOutcome measuresParkinson's diseaseDe novo Parkinson's diseaseMDS-UPDRSItem-level dataFrequency of ESSymptomatic medicationsFrequent administrationMonths of observationEfficacy assessmentDisease progressionSymptom emergenceRating ScaleItem responsesIb and IIUrate elevationTrialsQuantification 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 ResearchAltmetricConceptsCentral 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 methodValidity of the Short Weekly Calendar Planning Activity in patients with Parkinson disease and nonmanifesting LRRK2 and GBA carriers
Schejter‐Margalit T, Binyamin N, Thaler A, Maidan I, Cedarbaum J, Orr‐Urtreger A, Weisz M, Goldstein O, Giladi N, Mirelman A, Kizony R. Validity of the Short Weekly Calendar Planning Activity in patients with Parkinson disease and nonmanifesting LRRK2 and GBA carriers. European Journal Of Neurology 2024, 31: e16327. PMID: 38743695, PMCID: PMC11235808, DOI: 10.1111/ene.16327.Peer-Reviewed Original ResearchCitationsConceptsKnown-groups validityWeekly Calendar Planning ActivityColor Trails TestActivities of Daily Living ScaleKnown-groups construct validityIdiopathic PDPhysical Activity ScaleDaily Living ScaleEngland Activities of Daily Living ScaleNonmanifesting carriersPD to healthy controlsIdiopathic PD groupMontreal Cognitive AssessmentEcological validitySE-ADLActivity ScaleCompare personsConstruct validityOutcome measuresConvergent validityCognitive AssessmentGBA carriersEngland ActivitiesParkinson's diseaseCognitive testsMild cognitive impairment among LRRK2 and GBA1 patients with Parkinson's disease
Thaler A, Livne V, Rubinstein E, Omer N, Faust-Socher A, Cohen B, Giladi N, Shirvan J, Cedarbaum J, Gana-Weisz M, Goldstein O, Orr-Urtreger A, Alcalay R, Mirelman A. Mild cognitive impairment among LRRK2 and GBA1 patients with Parkinson's disease. Parkinsonism & Related Disorders 2024, 123: 106970. PMID: 38691978, DOI: 10.1016/j.parkreldis.2024.106970.Peer-Reviewed Original ResearchCitationsAltmetricConceptsMild cognitive impairmentIdiopathic PDMovement Disorder SocietyIncidence of mild cognitive impairmentFrequency of mild cognitive impairmentDiagnosis of mild cognitive impairmentCognitive impairmentLRRK2-PDLevel I criteriaParkinson's diseaseLevel II criteriaCarriers of mutationsMotor symptom onsetHoehn and YahrGBA1-PDCognitive batteryGender-matched controlsCognitive domainsEarly-stage PDI criteriaClinical characteristicsPD cohortDisorder SocietySymptom onsetHealthy adultsThe ALSFRS-R Summit: a global call to action on the use of the ALSFRS-R in ALS clinical trials
Genge A, Cedarbaum J, Shefner J, Chio A, Al-Chalabi A, Van Damme P, McDermott C, Glass J, Berry J, van Eijk R, Fournier C, Grosskreutz J, Andrews J, Bertone V, Bunte T, Couillard M, Cummings C, Kittle G, Polzer J, Salmon K, Straub C, van den Berg L. The ALSFRS-R Summit: a global call to action on the use of the ALSFRS-R in ALS clinical trials. Amyotrophic Lateral Sclerosis And Frontotemporal Degeneration 2024, 25: 382-387. PMID: 38396337, DOI: 10.1080/21678421.2024.2320880.Peer-Reviewed Original ResearchCitationsConceptsAmyotrophic Lateral Sclerosis Functional Rating ScaleALSFRS-RClinical trialsStatistical analysis planMonitor functional changesRating ScaleOutcome measuresFunctional Rating ScalePrimary outcome measureClinical trial designALS clinical trialsFunctional changesTrial designTrialsClinical trialistsScaleALS trialsCinpanemab 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsDisease 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
2023
Digital Mobility Measures: A Window into Real‐World Severity and Progression of Parkinson's Disease
Mirelman A, Volkov J, Salomon A, Gazit E, Nieuwboer A, Rochester L, Del Din S, Avanzino L, Pelosin E, Bloem B, Della Croce U, Cereatti A, Thaler A, Roggen D, Mazza C, Shirvan J, Cedarbaum J, Giladi N, Hausdorff J. Digital Mobility Measures: A Window into Real‐World Severity and Progression of Parkinson's Disease. Movement Disorders 2023, 39: 328-338. PMID: 38151859, DOI: 10.1002/mds.29689.Peer-Reviewed Original ResearchCitationsAltmetricRelative 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 ResearchMeSH Keywords and ConceptsConceptsEarly 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 functioningMapping Relevance of Digital Measures to Meaningful Symptoms and Impacts in Early 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. Mapping Relevance of Digital Measures to Meaningful Symptoms and Impacts in Early Parkinson’s Disease. Journal Of Parkinson's Disease 2023, 13: 589-607. PMID: 37212073, PMCID: PMC10357170, DOI: 10.3233/jpd-225122.Peer-Reviewed Original ResearchCitationsAltmetricMeSH KeywordsThe 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 ResearchCitationsAltmetricConceptsDiagnosis 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
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