2022
The CELLO trial: Protocol of a planned phase 4 study to assess the efficacy of Ocrelizumab in patients with radiologically isolated syndrome
Longbrake EE, Hua LH, Mowry EM, Gauthier SA, Alvarez E, Cross AH, Pei J, Priest J, Raposo C, Hafler DA, Winger RC. The CELLO trial: Protocol of a planned phase 4 study to assess the efficacy of Ocrelizumab in patients with radiologically isolated syndrome. Multiple Sclerosis And Related Disorders 2022, 68: 104143. PMID: 36031693, PMCID: PMC9772048, DOI: 10.1016/j.msard.2022.104143.Peer-Reviewed Original ResearchConceptsEfficacy of ocrelizumabMultiple sclerosisImmunologic biomarkersClinical trialsTransient B-cell depletionClinical multiple sclerosisCSF immune cellsEffects of ocrelizumabMS disease pathophysiologyNew brain lesionsOvert neurological symptomsB-cell depletionPlacebo-controlled studyPhase 4 studyLong-term outcomesPatient-reported outcomesPrimary progressive MSHumanized monoclonal antibodyFirst-degree relativesB cell biologySubtle cognitive impairmentEligible patientsImmune recoveryProgressive MSWeek 48
2020
B Cells, T Cells and Inflammatory CSF Biomarkers in Primary Progressive MS and Relapsing MS in the OBOE (Ocrelizumab Biomarker Outcome Evaluation) Trial (1635)
Bar-Or A, Bennett J, Von Budingen H, Carruthers R, Edwards K, Fallis R, Fiore D, Gelfand J, Giacomini P, Greenberg B, Hafler D, Longbrake E, Assman B, Ionete C, Kaunzner U, Lock C, Ma X, Musch B, Pardo G, Pei J, Piehl F, Weber M, Ziemssen T, Herman A, Harp C, Cross A. B Cells, T Cells and Inflammatory CSF Biomarkers in Primary Progressive MS and Relapsing MS in the OBOE (Ocrelizumab Biomarker Outcome Evaluation) Trial (1635). Neurology 2020, 94 DOI: 10.1212/wnl.94.15_supplement.1635.Peer-Reviewed Original Research
2019
Siponimod Chips Away at Progressive MS
Longbrake EE, Hafler DA. Siponimod Chips Away at Progressive MS. Cell 2019, 179: 1440. PMID: 31951523, PMCID: PMC8023412, DOI: 10.1016/j.cell.2019.11.034.Peer-Reviewed Original ResearchConceptsProgressive multiple sclerosisGadolinium-enhancing MRI lesionsInflammatory disease activityImmunomodulatory medicationsDisability progressionDisease activityMRI lesionsProgressive MSNeurologic disabilityPMS patientsMultiple sclerosisSiponimodMedicationsSclerosisPatientsLesionsBedsideProgression
2003
Activated CD8+ T cells in secondary progressive MS secrete lymphotoxin
Buckle GJ, Höllsberg P, Hafler DA. Activated CD8+ T cells in secondary progressive MS secrete lymphotoxin. Neurology 2003, 60: 702-705. PMID: 12601116, DOI: 10.1212/01.wnl.0000048204.89346.30.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntibodiesCD3 ComplexCD8-Positive T-LymphocytesCell DivisionCell SeparationCells, CulturedCytokinesFemaleFlow CytometryGene FrequencyHumansLymphotoxin-alphaMaleMiddle AgedMultiple Sclerosis, Chronic ProgressiveMultiple Sclerosis, Relapsing-RemittingPolymorphism, Single NucleotideReference ValuesConceptsT cellsNormal controlsSecondary progressive MSCytokine secretion profileFunctional activation statesLymphotoxin secretionProgressive MSActivated CD8Cytokine secretionSecretion profileCytokine genesCD8SecretionSignificant differencesPatientsSignificant increaseActivation stateSingle nucleotide polymorphism analysisPolymorphism analysisNucleotide polymorphism analysisCells
1993
Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the Northeast Cooperative Multiple Sclerosis Treatment Group.
Weiner HL, Mackin GA, Orav EJ, Hafler DA, Dawson DM, LaPierre Y, Herndon R, Lehrich JR, Hauser SL, Turel A, Fisher M, Birnbaum G, McArthur J, Butler R, Moore M, Sigsbee B, Safran A. Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the Northeast Cooperative Multiple Sclerosis Treatment Group. Neurology 1993, 43: 910-8. PMID: 8388090, DOI: 10.1212/wnl.43.5.910.Peer-Reviewed Original ResearchConceptsMajority of patientsInduction regimenTreatment failureTreatment groupsCyclophosphamide pulse therapyPatients 40 yearsPatients ages 41Progressive MS patientsPulse cyclophosphamide therapyPatients age 18Progressive multiple sclerosisNonbooster groupPulse therapyCyclophosphamide therapyProgressive MSMS patientsMultiple sclerosisDisease progressionSignificant benefitsAge 41Subsequent progressionPatientsInitial stabilizationAge 18Regimen
1988
Oligoclonal T lymphocytes in the cerebrospinal fluid of patients with multiple sclerosis.
Hafler DA, Duby AD, Lee SJ, Benjamin D, Seidman JG, Weiner HL. Oligoclonal T lymphocytes in the cerebrospinal fluid of patients with multiple sclerosis. Journal Of Experimental Medicine 1988, 167: 1313-1322. PMID: 3258624, PMCID: PMC2188923, DOI: 10.1084/jem.167.4.1313.Peer-Reviewed Original ResearchConceptsT cell clonesT cell populationsOligoclonal T-cell populationsTCR gene rearrangement patternsCerebrospinal fluidGene rearrangement patternsCell clonesT cellsRearrangement patternsChronic progressive multiple sclerosis patientsProgressive multiple sclerosis patientsCell populationsChronic progressive MSHerpes zoster meningoencephalitisOligoclonal T lymphocytesOligoclonal T cellsT cell responsesMultiple sclerosis patientsCentral nervous systemT cell receptor beta chainTCR gene rearrangementsIndividual T cellsProgressive MSGamma chain geneImmune compartment
1986
Immunologic responses of progressive multiple sclerosis patients treated with an anti-T-cell monoclonal antibody, anti-T12.
Hafler D, Fallis R, Dawson D, Schlossman S, Reinherz E, Weiner H. Immunologic responses of progressive multiple sclerosis patients treated with an anti-T-cell monoclonal antibody, anti-T12. Neurology 1986, 36: 777-84. PMID: 3486383, DOI: 10.1212/wnl.36.6.777.Peer-Reviewed Original ResearchConceptsHuman anti-mouse antibodiesAnti-mouse antibodiesDay 3Anti-T cell monoclonal antibodiesProgressive multiple sclerosis patientsPost-thymic T cellsMultiple sclerosis patientsMild allergic reactionsProgression of diseaseMonoclonal Antibodies ReactiveEffect of treatmentPhase one studyProgressive MSClinical effectsSclerosis patientsImmunologic responseBlood levelsImmunologic studiesPokeweed mitogenAllergic reactionsT cellsAntibody reactivePatientsDay 1Day 7