2024
Siponimod Attenuates Neuronal Cell Death Triggered by Neuroinflammation via NFκB and Mitochondrial Pathways
Gurrea-Rubio M, Wang Q, Mills E, Wu Q, Pitt D, Tsou P, Fox D, Mao-Draayer Y. Siponimod Attenuates Neuronal Cell Death Triggered by Neuroinflammation via NFκB and Mitochondrial Pathways. International Journal Of Molecular Sciences 2024, 25: 2454. PMID: 38473703, PMCID: PMC10931690, DOI: 10.3390/ijms25052454.Peer-Reviewed Original ResearchConceptsSecondary progressive MSRelapsing-remitting MSCentral nervous systemMultiple sclerosisProgressive MSModulator of sphingosine-1-phosphateCytokine tumor necrosis factor-alphaEffects of siponimodTumor necrosis factor-alphaHeterogeneous clinical courseBouts of inflammationNeuroprotective effectsPreclinical animal modelsAutoimmune demyelinating diseaseNecrosis factor-alphaMitochondrial oxidative phosphorylationHuman induced pluripotent stem cell (iPSC)-derived neuronsSphingosine-1-phosphateCytokine signaling pathwaysClinical courseLive cell analysisProgressive diseaseOral treatmentMitochondrial pathwayFactor-alpha
2022
Toward Precision Phenotyping of Multiple Sclerosis
Pitt D, Lo CH, Gauthier SA, Hickman RA, Longbrake E, Airas LM, Mao-Draayer Y, Riley C, De Jager PL, Wesley S, Boster A, Topalli I, Bagnato F, Mansoor M, Stuve O, Kister I, Pelletier D, Stathopoulos P, Dutta R, Lincoln MR. Toward Precision Phenotyping of Multiple Sclerosis. Neurology Neuroimmunology & Neuroinflammation 2022, 9: e200025. PMID: 36041861, PMCID: PMC9427000, DOI: 10.1212/nxi.0000000000200025.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersDisease ProgressionHumansInflammationMultiple SclerosisMultiple Sclerosis, Chronic ProgressiveNervous System DiseasesConceptsMultiple sclerosisSecondary progressive multiple sclerosisPathological processesProgressive multiple sclerosisKey pathological processClinical trial designDevelopment of biomarkersPerilesional inflammationNeuroaxonal degenerationMS phenotypeTrial designClinical importancePersonalized careM phenotypeSclerosisPhenotypeRemyelinationInflammationSyndromePrognosticationDegenerationProgressionBiomarkersCareClinical trials in multiple sclerosis: past, present, and future
Manouchehri N, Shirani A, Salinas VH, Tardo L, Hussain RZ, Pitt D, Stuve O. Clinical trials in multiple sclerosis: past, present, and future. Neurologia I Neurochirurgia Polska 2022, 56: 228-235. PMID: 35712986, DOI: 10.5603/pjnns.a2022.0041.Peer-Reviewed Original ResearchConceptsDisease-modifying therapiesMultiple sclerosisClinical trialsManagement of MSEffective disease-modifying therapiesDisability Assessment ScaleDisease-specific interventionsDisease diagnostic criteriaBurden of diseaseClinical trial developmentDisease-specific biomarkersMS pathophysiologyDiagnostic criteriaClinical practiceTrial developmentAssessment ScaleSclerosisTrialsPatientsNeuroimmunologyPathophysiologyTherapyDiseaseDiagnosisContinued progressMagnetic Susceptibility Source Separation Solely from Gradient Echo Data: Histological Validation
Dimov AV, Gillen KM, Nguyen TD, Kang J, Sharma R, Pitt D, Gauthier SA, Wang Y. Magnetic Susceptibility Source Separation Solely from Gradient Echo Data: Histological Validation. Tomography 2022, 8: 1544-1551. PMID: 35736875, PMCID: PMC9228115, DOI: 10.3390/tomography8030127.Peer-Reviewed Original ResearchSusceptibility source separation from gradient echo data using magnitude decay modeling
Dimov AV, Nguyen TD, Gillen KM, Marcille M, Spincemaille P, Pitt D, Gauthier SA, Wang Y. Susceptibility source separation from gradient echo data using magnitude decay modeling. Journal Of Neuroimaging 2022, 32: 852-859. PMID: 35668022, DOI: 10.1111/jon.13014.Peer-Reviewed Original Research
2021
QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions
Gillen KM, Mubarak M, Park C, Ponath G, Zhang S, Dimov A, Levine‐Ritterman M, Toro S, Huang W, Amici S, Kaunzner UW, Gauthier SA, Guerau‐de‐Arellano M, Wang Y, Nguyen TD, Pitt D. QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions. Annals Of Clinical And Translational Neurology 2021, 8: 877-886. PMID: 33704933, PMCID: PMC8045922, DOI: 10.1002/acn3.51338.Peer-Reviewed Original ResearchConceptsNormal-appearing white matterMyeloid cellsLesion rimReactive oxygen speciesQuantitative susceptibility mappingChronic active lesionsChronic glial activationPro-inflammatory cytokinesBlood-brain barrierWhite matter lesionsAdjacent normal-appearing white matterMultiple sclerosis lesionsGlial activationActivated microgliaHistopathological correlatesChronic inflammationActive lesionsCytokine productionMatter lesionsMS lesionsWhite matterHuman-induced pluripotent stem cellsSclerosis lesionsLesionsLesion perimeter
2020
Differential expression of the T-cell inhibitor TIGIT in glioblastoma and MS
Lucca LE, Lerner BA, Park C, DeBartolo D, Harnett B, Kumar VP, Ponath G, Raddassi K, Huttner A, Hafler DA, Pitt D. Differential expression of the T-cell inhibitor TIGIT in glioblastoma and MS. Neurology Neuroimmunology & Neuroinflammation 2020, 7: e712. PMID: 32269065, PMCID: PMC7188477, DOI: 10.1212/nxi.0000000000000712.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCentral Nervous System NeoplasmsFemaleGlioblastomaHumansMaleMiddle AgedMultiple SclerosisReceptors, ImmunologicUp-RegulationConceptsTumor-infiltrating T cellsT cellsPD-1/PD-L1Anti-TIGIT therapyExpression of CD226Expression of TIGITPostmortem CNS tissueLymphocytes of patientsFresh surgical resectionsLigand CD155TIGIT expressionSurgical resectionPD-1PD-L1CNS diseaseHealthy controlsHealthy donorsLymphocytic expressionImmune responseCNS tissueMS lesionsTIGITImmune pathwaysPatientsGlioblastoma multiforme
2019
Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry
Ramaglia V, Sheikh-Mohamed S, Legg K, Park C, Rojas OL, Zandee S, Fu F, Ornatsky O, Swanson EC, Pitt D, Prat A, McKee TD, Gommerman JL. Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry. ELife 2019, 8: e48051. PMID: 31368890, PMCID: PMC6707785, DOI: 10.7554/elife.48051.Peer-Reviewed Original ResearchMeSH KeywordsAdultFemaleHumansImage CytometryImmunologic FactorsLeukocytesMultiple SclerosisNatalizumabProteinsConceptsMultiple sclerosisMS disease activityT-cell phenotypeMass cytometryTypes of lymphocytesMultiple sclerosis lesionsNatalizumab cessationDisease activityMS patientsInflammatory lesionsImmune cellsSpinal cordLesion morphometryMS lesionsB cellsLesion typeSclerosis lesionsLesionsBlood vesselsCell phenotypeFunctional stateCytometryCellular contentCell-cell interactionsPhenotype
2018
Enhanced astrocyte responses are driven by a genetic risk allele associated with multiple sclerosis
Ponath G, Lincoln MR, Levine-Ritterman M, Park C, Dahlawi S, Mubarak M, Sumida T, Airas L, Zhang S, Isitan C, Nguyen TD, Raine CS, Hafler DA, Pitt D. Enhanced astrocyte responses are driven by a genetic risk allele associated with multiple sclerosis. Nature Communications 2018, 9: 5337. PMID: 30559390, PMCID: PMC6297228, DOI: 10.1038/s41467-018-07785-8.Peer-Reviewed Original ResearchConceptsMultiple sclerosisAstrocyte responseRisk variantsLocal autoimmune inflammationPeripheral immune cellsCentral nervous system cellsPeripheral immune systemCultured human astrocytesNervous system cellsNF-κB signalingCNS accessDysfunctional lymphocytesAstroglial functionAutoimmune inflammationLymphocytic infiltrateLymphocyte recruitmentImmune cellsGenetic risk allelesGenetic risk variantsMS lesionsMS susceptibilityHuman astrocytesLesion sizeImmune systemSystem cellsQuantitative susceptibility mapping identifies inflammation in a subset of chronic multiple sclerosis lesions
Kaunzner UW, Kang Y, Zhang S, Morris E, Yao Y, Pandya S, Rua S, Park C, Gillen KM, Nguyen TD, Wang Y, Pitt D, Gauthier SA. Quantitative susceptibility mapping identifies inflammation in a subset of chronic multiple sclerosis lesions. Brain 2018, 142: 133-145. PMID: 30561514, PMCID: PMC6308309, DOI: 10.1093/brain/awy296.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntigens, CDAntigens, Differentiation, MyelomonocyticBrainCarbon RadioisotopesChronic DiseaseCross-Sectional StudiesFemaleHumansInflammationIronIsoquinolinesMacrophagesMagnetic Resonance ImagingMaleMicrogliaMiddle AgedMultiple SclerosisPositron-Emission TomographyRetrospective StudiesYoung AdultConceptsChronic active lesionsMultiple sclerosisChronic lesionsActive lesionsMultiple sclerosis lesionsHyperintense rimQuantitative susceptibility mappingChronic active multiple sclerosis lesionsSclerosis lesionsChronic multiple sclerosis lesionsActive multiple sclerosis lesionsPersistent inflammatory activityProgressive multiple sclerosisMicroglia/macrophagesInnate immune activationEarly disease stagesTranslocator proteinGreater tissue damagePost-mortem studiesProgressive patientsActivated microgliaInflammatory activityPersistent inflammationImmune activationDisease stageAstrocytes play a crucial role in the formation and evolution of MS lesions – Yes
Pitt D, Ponath G. Astrocytes play a crucial role in the formation and evolution of MS lesions – Yes. Multiple Sclerosis Journal 2018, 25: 15-17. PMID: 30136895, DOI: 10.1177/1352458518793026.Peer-Reviewed Original ResearchMagnetic susceptibility increases as diamagnetic molecules breakdown: Myelin digestion during multiple sclerosis lesion formation contributes to increase on QSM
Deh K, Ponath GD, Molvi Z, Parel G, Gillen KM, Zhang S, Nguyen TD, Spincemaille P, Ma Y, Gupta A, Gauthier SA, Pitt D, Wang Y. Magnetic susceptibility increases as diamagnetic molecules breakdown: Myelin digestion during multiple sclerosis lesion formation contributes to increase on QSM. Journal Of Magnetic Resonance Imaging 2018, 48: 1281-1287. PMID: 29517817, PMCID: PMC6129234, DOI: 10.1002/jmri.25997.Peer-Reviewed Original ResearchThe Role of Astrocytes in Multiple Sclerosis
Ponath G, Park C, Pitt D. The Role of Astrocytes in Multiple Sclerosis. Frontiers In Immunology 2018, 9: 217. PMID: 29515568, PMCID: PMC5826071, DOI: 10.3389/fimmu.2018.00217.Peer-Reviewed Original ResearchMeSH KeywordsAstrocytesBlood-Brain BarrierCentral Nervous SystemHumansImmunosuppressive AgentsMultiple SclerosisSignal TransductionConceptsRole of astrocytesImmune cell accessCentral nervous systemMultiple sclerosis lesionsAstrocyte activationMultiple sclerosisGlial scarAstrocyte functionMS treatmentMS lesionsNervous systemAstrocytesSclerosis lesionsLesion formationFunctional polarizationLesionsCell accessSclerosisInflammationPathogenesisSignificance and In Vivo Detection of Iron-Laden Microglia in White Matter Multiple Sclerosis Lesions
Gillen KM, Mubarak M, Nguyen TD, Pitt D. Significance and In Vivo Detection of Iron-Laden Microglia in White Matter Multiple Sclerosis Lesions. Frontiers In Immunology 2018, 9: 255. PMID: 29515576, PMCID: PMC5826076, DOI: 10.3389/fimmu.2018.00255.Peer-Reviewed Original ResearchConceptsCentral nervous systemChronic active lesionsMultiple sclerosisActive lesionsWhite matterWhite matter MS lesionsQuantitative susceptibility mappingNovel MS therapiesResident immune cellsChronic inflammatory activityWhite matter lesionsMyeloid cell activationAdjacent white matterWhite matter multiple sclerosis lesionsChronic tissue damageMultiple sclerosis lesionsMS therapyInflammatory activityMagnetic resonance imaging techniquesChronic inflammationMatter lesionsAged brainImmune cellsMyelin phagocytosisChronic diseasesMyeloid cell plasticity in the evolution of central nervous system autoimmunity
Giles DA, Washnock‐Schmid J, Duncker PC, Dahlawi S, Ponath G, Pitt D, Segal BM. Myeloid cell plasticity in the evolution of central nervous system autoimmunity. Annals Of Neurology 2018, 83: 131-141. PMID: 29283442, PMCID: PMC5876132, DOI: 10.1002/ana.25128.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArginaseAutoimmune Diseases of the Nervous SystemBone Marrow CellsCell PlasticityChimeraDisease ProgressionEncephalomyelitis, Autoimmune, ExperimentalHumansImmunohistochemistryLectins, C-TypeMannose ReceptorMannose-Binding LectinsMiceMice, Inbred C57BLMultiple SclerosisMyeloid CellsNitric Oxide Synthase Type IIPhenotypeReceptors, Cell SurfaceConceptsInducible nitric oxide synthaseExperimental autoimmune encephalomyelitisCNS myeloid cellsCentral nervous systemCentral nervous system autoimmunityChronic active MS lesionsActive MS lesionsMultiple sclerosisMyeloid cellsMS lesionsAnimal model experimental autoimmune encephalomyelitisRemission of EAEModel experimental autoimmune encephalomyelitisMyeloid cell plasticityEncephalitogenic T cellsNitric oxide synthaseMyeloid cell phenotypeFuture therapeutic strategiesHuman myeloid cellsAnn NeurolNoninflammatory phenotypePolarized subsetsClinical remissionAutoimmune encephalomyelitisProinflammatory markers
2016
Quantitative Susceptibility Mapping and R2* Measured Changes during White Matter Lesion Development in Multiple Sclerosis: Myelin Breakdown, Myelin Debris Degradation and Removal, and Iron Accumulation
Zhang Y, Gauthier SA, Gupta A, Chen W, Comunale J, Chiang G, Zhou D, Askin G, Zhu W, Pitt D, Wang Y. Quantitative Susceptibility Mapping and R2* Measured Changes during White Matter Lesion Development in Multiple Sclerosis: Myelin Breakdown, Myelin Debris Degradation and Removal, and Iron Accumulation. American Journal Of Neuroradiology 2016, 37: 1629-1635. PMID: 27256856, PMCID: PMC5018433, DOI: 10.3174/ajnr.a4825.Peer-Reviewed Original ResearchMeSH KeywordsAdultFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedMultiple SclerosisMyelin SheathWhite MatterConceptsMyelin breakdownQuantitative susceptibility mappingExpanded Disability Status Scale scoreEarly active MS lesionsDisability Status Scale scoreIron accumulationDifferent enhancing patternStatus Scale scoreActive MS lesionsWhite matter lesionsMultiple sclerosis lesionsDisease durationChronic lesionsEarly chronicMatter lesionsMultiple sclerosisActive lesionsMyelin debrisMS lesionsLesion changesScale scoreLesion typeSclerosis lesionsLesionsLesion developmentIron in Multiple Sclerosis and Its Noninvasive Imaging with Quantitative Susceptibility Mapping
Stüber C, Pitt D, Wang Y. Iron in Multiple Sclerosis and Its Noninvasive Imaging with Quantitative Susceptibility Mapping. International Journal Of Molecular Sciences 2016, 17: 100. PMID: 26784172, PMCID: PMC4730342, DOI: 10.3390/ijms17010100.Peer-Reviewed Original ResearchConceptsMultiple sclerosisMagnetic resonance imagingBrain tissueQuantitative susceptibility mappingMS brain tissueAdvanced MRI methodsMS patientsChronic inflammationImmunohistochemical investigationBrain ironMyeloid cellsResonance imagingNon-invasive studyHistological studyRole of ironOxidative stressNoninvasive imagingSclerosisInflammationCellular distributionMRI methodsNeurodegenerationTissueImagingPatients
2015
Basal Ganglia Iron in Patients with Multiple Sclerosis Measured with 7T Quantitative Susceptibility Mapping Correlates with Inhibitory Control
Schmalbrock P, Prakash RS, Schirda B, Janssen A, Yang GK, Russell M, Knopp MV, Boster A, Nicholas JA, Racke M, Pitt D. Basal Ganglia Iron in Patients with Multiple Sclerosis Measured with 7T Quantitative Susceptibility Mapping Correlates with Inhibitory Control. American Journal Of Neuroradiology 2015, 37: 439-446. PMID: 26611996, PMCID: PMC7960135, DOI: 10.3174/ajnr.a4599.Peer-Reviewed Original ResearchBiomarkers in multiple sclerosis
Housley WJ, Pitt D, Hafler DA. Biomarkers in multiple sclerosis. Clinical Immunology 2015, 161: 51-58. PMID: 26143623, DOI: 10.1016/j.clim.2015.06.015.Peer-Reviewed Original ResearchConceptsMultiple sclerosisB cell chemoattractant CXCL13Myelin-reactive T cellsMacrophage marker CD163Reactive T cellsMarkers of neurodegenerationKIR4.1 antibodiesMS seraClinical outcomesOligoclonal bandsYKL-40Disease progressionT cellsMS susceptibilityCerebrospinal fluidPotential biomarkersViral titersClinical useBiomarkersBiomarker researchSclerosisProgressionDisease diagnosisCD163CXCL13Concise Review: Modeling Multiple Sclerosis With Stem Cell Biological Platforms: Toward Functional Validation of Cellular and Molecular Phenotypes in Inflammation-Induced Neurodegeneration
Orack JC, Deleidi M, Pitt D, Mahajan K, Nicholas JA, Boster AL, Racke MK, Comabella M, Watanabe F, Imitola J. Concise Review: Modeling Multiple Sclerosis With Stem Cell Biological Platforms: Toward Functional Validation of Cellular and Molecular Phenotypes in Inflammation-Induced Neurodegeneration. Stem Cells Translational Medicine 2015, 4: 252-260. PMID: 25593207, PMCID: PMC4339849, DOI: 10.5966/sctm.2014-0133.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsClinical Trials, Phase I as TopicHumansInflammationModels, BiologicalMultiple SclerosisNeural Stem CellsOligodendrogliaConceptsSomatic cell reprogrammingStem cellsInduced pluripotent stem cell (iPSC) technologyPluripotent stem cell (iPSC) technologyOligodendrocyte progenitor cellsMultiple sclerosisGeneration of neuronsNew mechanistic insightsCell reprogrammingNovel stem cellFunctional validationStem cell technologyMolecular mechanismsBiological toolsMesenchymal stem cellsMolecular phenotypesNovel mechanismProgenitor cellsImmune cell functionPhase I clinical trialMechanistic insightsBiological platformCell functionSignificant unmet needBrain atrophy