2024
CNS cell-derived exosome signatures as blood-based biomarkers of neurodegenerative diseases
Park C, Weerakkody J, Schneider R, Miao S, Pitt D. CNS cell-derived exosome signatures as blood-based biomarkers of neurodegenerative diseases. Frontiers In Neuroscience 2024, 18: 1426700. PMID: 38966760, PMCID: PMC11222337, DOI: 10.3389/fnins.2024.1426700.Peer-Reviewed Original ResearchNeurodegenerative diseasesSubtype of extracellular vesiclesDisease-related processesDisease-associated changesCentral nervous systemBlood-based proteinsBiomarkers of neurodegenerative diseasesBlood-brain barrierCell typesExosome populationMolecular cargoExtracellular vesiclesCell of originRNA biomarkersExosome isolationTranslation to clinical useCell-derived exosomesLack of standardized methodologyMolecular contentExosomesBlood-based biomarkersPeripheral bloodCellsExosome signatureMolecular biomarkersSiponimod 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-alphaImaging chronic active lesions in multiple sclerosis: a consensus statement
Bagnato F, Sati P, Hemond C, Elliott C, Gauthier S, Harrison D, Mainero C, Oh J, Pitt D, Shinohara R, Smith S, Trapp B, Azevedo C, Calabresi P, Henry R, Laule C, Ontaneda D, Rooney W, Sicotte N, Reich D, Absinta M. Imaging chronic active lesions in multiple sclerosis: a consensus statement. Brain 2024, 147: 2913-2933. PMID: 38226694, PMCID: PMC11370808, DOI: 10.1093/brain/awae013.Peer-Reviewed Original ResearchChronic active lesionsMagnetic resonance imagingConsensus statementMultiple sclerosisActive lesionsManifestations of chronic inflammationParamagnetic rim lesionsMRI-definedNorth American ImagingRadiological definitionChronic inflammationRim lesionsClinical translationLesionsResonance imagingMRI sequencesIn vivoT1-wBrains of personsBiomarkers
2023
Pathological Validation of Multiple Sclerosis Lesion Rims on Phase and Quantitative Susceptibility Mapping (QSM) images
Gillen K, Nguyen T, Dimov A, Demmon E, Kovanlikaya I, Bagnato F, Romano D, Pitt D, Gauthier S, Wang Y. Pathological Validation of Multiple Sclerosis Lesion Rims on Phase and Quantitative Susceptibility Mapping (QSM) images. Proceedings Of The International Society For Magnetic Resonance In Medicine ... Scientific Meeting And Exhibition. 2023 DOI: 10.58530/2023/0035.Peer-Reviewed Original ResearchImaging Chronic Active Lesions in Multiple Sclerosis: a Consensus Statement from the North America Imaging in Multiple Sclerosis Cooperative (P11-3.009)
Bagnato F, Sati P, Hemond C, Elliott C, Gauthier S, Harrison D, Mainero C, Oh J, Pitt D, Shinohara R, Smith S, Bruce T, Azevedo C, Calabresi P, Henry R, Laule C, Ontaneda D, Rooney W, Sicotte N, Reich D, Absinta M. Imaging Chronic Active Lesions in Multiple Sclerosis: a Consensus Statement from the North America Imaging in Multiple Sclerosis Cooperative (P11-3.009). Neurology 2023, 100 DOI: 10.1212/wnl.0000000000203168.Peer-Reviewed Original Research
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 ResearchConceptsMultiple 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 ResearchEfficacy of Disease Modifying Therapies in Progressive MS and How Immune Senescence May Explain Their Failure
Manouchehri N, Salinas VH, Yeganeh N, Pitt D, Hussain RZ, Stuve O. Efficacy of Disease Modifying Therapies in Progressive MS and How Immune Senescence May Explain Their Failure. Frontiers In Neurology 2022, 13: 854390. PMID: 35432156, PMCID: PMC9009145, DOI: 10.3389/fneur.2022.854390.Peer-Reviewed Original ResearchProgressive multiple sclerosisSecondary progressive MSMultiple sclerosisImmune senescenceSecondary progressive multiple sclerosisDifferent MS phenotypesDisease-Modifying TherapiesSuccessful clinical managementAge-related factorsAdvent of diseaseModifying therapiesProgressive MSRelapse frequencyClinical managementImmune responseDistinct pathogenesesImmune systemM phenotypeDisease transitionTherapyMain correlatesDisease phenotypePatientsRRMSSignal changesDimethyl Fumarate Reduces Inflammation in Chronic Active Multiple Sclerosis Lesions
Zinger N, Ponath G, Sweeney E, Nguyen TD, Lo CH, Diaz I, Dimov A, Teng L, Zexter L, Comunale J, Wang Y, Pitt D, Gauthier SA. Dimethyl Fumarate Reduces Inflammation in Chronic Active Multiple Sclerosis Lesions. Neurology Neuroimmunology & Neuroinflammation 2022, 9: e1138. PMID: 35046083, PMCID: PMC8771666, DOI: 10.1212/nxi.0000000000001138.Peer-Reviewed Original ResearchConceptsChronic active lesionsGlatiramer acetateRim lesionsHuman microgliaDimethyl fumarateMultiple sclerosisActive lesionsChronic active multiple sclerosis lesionsEffects of DMFActive multiple sclerosis lesionsClass III evidenceMarkers of inflammationRelapsing-remitting MSRetrospective observational studyQuantitative susceptibility mappingMultiple sclerosis lesionsActivation stateTreatment-induced changesMRI quantitative susceptibility mappingMicroglial activityGlial activityInflammatory activationMicroglial cellsObservational studyMS lesions
2021
Tet2 Controls the Responses of β cells to Inflammation in Autoimmune Diabetes
Rui J, Deng S, Perdigoto AL, Ponath G, Kursawe R, Lawlor N, Sumida T, Levine-Ritterman M, Stitzel ML, Pitt D, Lu J, Herold KC. Tet2 Controls the Responses of β cells to Inflammation in Autoimmune Diabetes. Nature Communications 2021, 12: 5074. PMID: 34417463, PMCID: PMC8379260, DOI: 10.1038/s41467-021-25367-z.Peer-Reviewed Original ResearchConceptsImmune cellsΒ-cellsNOD/SCID recipientsDiabetogenic immune cellsDiabetogenic T cellsBone marrow transplantType 1 diabetesExpression of TET2Human β-cellsIslet infiltratesSCID recipientsMarrow transplantInflammatory pathwaysTransfer of diseaseT cellsInflammatory genesImmune killingPathologic interactionsReduced expressionDiabetesInflammationTET2MiceRecipientsCellsAstrocyte Heterogeneity in Multiple Sclerosis: Current Understanding and Technical Challenges
Lo CH, Skarica M, Mansoor M, Bhandarkar S, Toro S, Pitt D. Astrocyte Heterogeneity in Multiple Sclerosis: Current Understanding and Technical Challenges. Frontiers In Cellular Neuroscience 2021, 15: 726479. PMID: 34456686, PMCID: PMC8385194, DOI: 10.3389/fncel.2021.726479.Peer-Reviewed Original ResearchIn vivo evidence of differential frontal cortex metabolic abnormalities in progressive and relapsing‐remitting multiple sclerosis
Swanberg KM, Prinsen H, DeStefano K, Bailey M, Kurada AV, Pitt D, Fulbright RK, Juchem C. In vivo evidence of differential frontal cortex metabolic abnormalities in progressive and relapsing‐remitting multiple sclerosis. NMR In Biomedicine 2021, 34: e4590. PMID: 34318959, DOI: 10.1002/nbm.4590.Peer-Reviewed Original ResearchConceptsProgressive multiple sclerosisRelapsing-remitting multiple sclerosisMultiple sclerosis patientsMultiple sclerosisDisease durationSclerosis patientsRelapsing-remitting multiple sclerosis patientsSignificant negative correlationAvailable disease-modifying therapiesFrontal cortex metabolismH-MRS protocolDisease-modifying therapiesHealthy control adultsN-acetyl aspartateCross-sectional analysisCortex metabolismMetabolic abnormalitiesΓ-aminobutyric acidMetabolites glutamateFrontal cortexSclerosisNegative correlationControl adultsGABAProton MRSQSM 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
Multiplex Imaging of Immune Cells in the Multiple Sclerosis Brain (4485)
Ramaglia V, Sheikh-Mohamed S, Legg K, Park C, Rojas O, Zandee S, Fu F, Ornatsky O, Swanson E, Pitt D, Prat A, McKee T, Gommerman J. Multiplex Imaging of Immune Cells in the Multiple Sclerosis Brain (4485). Neurology 2020, 94 DOI: 10.1212/wnl.94.15_supplement.4485.Peer-Reviewed Original ResearchDifferential 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 ResearchConceptsTumor-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
Quantifying the Metabolic Signature of Multiple Sclerosis by in vivo Proton Magnetic Resonance Spectroscopy: Current Challenges and Future Outlook in the Translation From Proton Signal to Diagnostic Biomarker
Swanberg KM, Landheer K, Pitt D, Juchem C. Quantifying the Metabolic Signature of Multiple Sclerosis by in vivo Proton Magnetic Resonance Spectroscopy: Current Challenges and Future Outlook in the Translation From Proton Signal to Diagnostic Biomarker. Frontiers In Neurology 2019, 10: 1173. PMID: 31803127, PMCID: PMC6876616, DOI: 10.3389/fneur.2019.01173.Peer-Reviewed Original ResearchMultiple sclerosisProton magnetic resonance spectroscopyDiagnostic biomarkersH-MRSStudy designVivo proton magnetic resonance spectroscopyCentral nervous system tissueNormal-appearing white matterNumerous metabolic alterationsPotential diagnostic biomarkersNervous system tissueMetabolic abnormalitiesH-MRS dataSpinal cordLesion compositionSclerosisMetabolic alterationsWhite matterGray matterMagnetic resonance spectroscopyMetabolic signaturesBiomarkersExperimental cohortLines of evidenceTechnical considerationsThe landscape of myeloid and astrocyte phenotypes in acute multiple sclerosis lesions
Park C, Ponath G, Levine-Ritterman M, Bull E, Swanson EC, De Jager PL, Segal BM, Pitt D. The landscape of myeloid and astrocyte phenotypes in acute multiple sclerosis lesions. Acta Neuropathologica Communications 2019, 7: 130. PMID: 31405387, PMCID: PMC6689891, DOI: 10.1186/s40478-019-0779-2.Peer-Reviewed Original ResearchConceptsMultiple sclerosis lesionsLesion rimAstrocyte phenotypeMyeloid cellsSclerosis lesionsActive multiple sclerosis lesionsAcute multiple sclerosis lesionsGlial activation markersActive MS lesionsNovel therapeutic targetDifferent lesion stagesPredominant cell typeAcute demyelinationDemyelinating lesionsCell typesActivation markersChronic inflammationDistinct myeloidCell-extrinsic factorsGlial cellsPhenotypic subsetsLesion stageGlial phenotypeMS lesionsLesion cellsMultiplexed 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 ResearchConceptsMultiple 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