2023
Development of neural repair therapy for chronic spinal cord trauma: soluble Nogo receptor decoy from discovery to clinical trial
Howard E, Strittmatter S. Development of neural repair therapy for chronic spinal cord trauma: soluble Nogo receptor decoy from discovery to clinical trial. Current Opinion In Neurology 2023, 36: 516-522. PMID: 37865850, PMCID: PMC10841037, DOI: 10.1097/wco.0000000000001205.Peer-Reviewed Original ResearchConceptsSpinal cord injuryChronic cervical spinal cord injuryCervical spinal cord injuryRecent clinical trialsCentral nervous systemClinical trialsAnimal studiesNeural repairChronic spinal cord injuryIncomplete spinal cord injuryTraumatic spinal cord injuryAdult mammalian central nervous systemContusion spinal cord injuryTreatment-naïve patientsSpinal cord traumaMammalian central nervous systemNeural repair therapiesUpper extremity strengthNonhuman primate studiesReceptor 1 pathwayNeurological recoveryNeurological deficitsCord traumaMedical therapyChronic stage
2020
Nogo receptor decoy promotes recovery and corticospinal growth in non-human primate spinal cord injury
Wang X, Zhou T, Maynard GD, Terse PS, Cafferty WB, Kocsis JD, Strittmatter SM. Nogo receptor decoy promotes recovery and corticospinal growth in non-human primate spinal cord injury. Brain 2020, 143: 1697-1713. PMID: 32375169, PMCID: PMC7850069, DOI: 10.1093/brain/awaa116.Peer-Reviewed Original ResearchConceptsPrimate spinal cord injurySpinal cord injuryCord injuryFemale African green monkeysTreatment-related adverse eventsChronic neurological deficitsNogo receptor 1Left motor cortexRecovery of functionPreclinical rodent modelsSpinal cord injury animalsAfrican green monkeysRaphespinal fibersAdverse eventsCervical cordNeurological deficitsSurgical complicationsCNS traumaTreatment cessationCorticospinal axonsLumbar catheterInjury animalsNeural recoverySpontaneous feedingLateral hemisection
2019
Plexina2 and CRMP2 Signaling Complex Is Activated by Nogo-A-Liganded Ngr1 to Restrict Corticospinal Axon Sprouting after Trauma
Sekine Y, Algarate PT, Cafferty WBJ, Strittmatter SM. Plexina2 and CRMP2 Signaling Complex Is Activated by Nogo-A-Liganded Ngr1 to Restrict Corticospinal Axon Sprouting after Trauma. Journal Of Neuroscience 2019, 39: 3204-3216. PMID: 30804090, PMCID: PMC6788813, DOI: 10.1523/jneurosci.2996-18.2019.Peer-Reviewed Original ResearchConceptsCNS traumaNeural repairMouse cervical spinal cordSpinal cord traumaCervical spinal cordNon-neuronal cellsInteraction of NogoAxon growth inhibitionAxonal guidance mechanismsNeurological recoveryAxonal sproutingCNS pathwaysCord traumaFunctional recoveryAxon sproutingSpinal cordNgR1 functionUnilateral pyramidotomyAxon regenerationAdult traumaNgR1TraumaAxon growthNogoCytoplasmic mediators
2018
Functional Genome-wide Screen Identifies Pathways Restricting Central Nervous System Axonal Regeneration
Sekine Y, Lin-Moore A, Chenette DM, Wang X, Jiang Z, Cafferty WB, Hammarlund M, Strittmatter SM. Functional Genome-wide Screen Identifies Pathways Restricting Central Nervous System Axonal Regeneration. Cell Reports 2018, 23: 415-428. PMID: 29642001, PMCID: PMC5937716, DOI: 10.1016/j.celrep.2018.03.058.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsCaenorhabditis elegansCaenorhabditis elegans ProteinsCentral Nervous SystemFemaleGene Regulatory NetworksGenomeMiceMice, Inbred C57BLMice, KnockoutNerve RegenerationOptic NerveRab GTP-Binding ProteinsRecovery of FunctionRetinal Ganglion CellsRNA InterferenceRNA, Small InterferingSpinal Cord InjuriesSuppressor of Cytokine Signaling ProteinsConceptsAxonal regenerationCentral nervous system axonal regenerationRetinal ganglion cell axon regenerationGreater motor functionOptic nerve crushCerebral cortical neuronsSpinal cord traumaNeurological recoveryCord traumaNerve crushCNS injuryAxonal regrowthCortical neuronsMotor functionAxon regenerationReceptor bindingComprehensive functional screenAdult mammalsInjuryMultiple pathwaysExpression profilesIdentifies pathwaysSignificant overlapPathwayFunction screen
2017
Regulation of axonal regeneration by the level of function of the endogenous Nogo receptor antagonist LOTUS
Hirokawa T, Zou Y, Kurihara Y, Jiang Z, Sakakibara Y, Ito H, Funakoshi K, Kawahara N, Goshima Y, Strittmatter SM, Takei K. Regulation of axonal regeneration by the level of function of the endogenous Nogo receptor antagonist LOTUS. Scientific Reports 2017, 7: 12119. PMID: 28935984, PMCID: PMC5608707, DOI: 10.1038/s41598-017-12449-6.Peer-Reviewed Original ResearchConceptsSpinal cord injuryOptic nerve crushAxonal regenerationMotor recoveryNerve crushNeural repairRetinal ganglion cell axonal regenerationAdult mammalian central nervous systemIntrinsic motor recoverySpontaneous neural repairAxonal growth inhibitorsMammalian central nervous systemCentral nervous systemNon-permissive environmentLevel of functionUntreated miceFunctional recoveryCord injuryReceptor antagonistNeuronal overexpressionNervous systemGenetic deletionViral overexpressionCrushInhibitors
2016
Inhibition of Poly-ADP-Ribosylation Fails to Increase Axonal Regeneration or Improve Functional Recovery after Adult Mammalian CNS Injury
Wang X, Sekine Y, Byrne AB, Cafferty WB, Hammarlund M, Strittmatter SM. Inhibition of Poly-ADP-Ribosylation Fails to Increase Axonal Regeneration or Improve Functional Recovery after Adult Mammalian CNS Injury. ENeuro 2016, 3: eneuro.0270-16.2016. PMID: 28032120, PMCID: PMC5187389, DOI: 10.1523/eneuro.0270-16.2016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsBenzimidazolesCells, CulturedCerebral CortexDisease Models, AnimalFemaleIsoenzymesMaleMice, 129 StrainMice, Inbred C57BLMice, TransgenicMotor ActivityNerve RegenerationOptic Nerve InjuriesPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsRecovery of FunctionSpinal Cord InjuriesThoracic VertebraeConceptsOptic nerve crush injuryNerve crush injuryThoracic spinal cordAxonal regenerationSpinal cordDorsal hemisectionCrush injuryFunctional recoveryPARP inhibitorsMotor function recoveryRecovery of functionPoly (ADP-ribose) polymeraseClinical PARP inhibitorsNeurological recoveryShort hairpin RNACNS traumaCNS injuryFunction recoveryAxonal regrowthSystemic administrationPharmacodynamic actionAxon regenerationTraumatic damageTherapeutic efficacyNeurological trauma
2015
Comprehensive Corticospinal Labeling with mu-crystallin Transgene Reveals Axon Regeneration after Spinal Cord Trauma in ngr1−/− Mice
Fink KL, Strittmatter SM, Cafferty WB. Comprehensive Corticospinal Labeling with mu-crystallin Transgene Reveals Axon Regeneration after Spinal Cord Trauma in ngr1−/− Mice. Journal Of Neuroscience 2015, 35: 15403-15418. PMID: 26586827, PMCID: PMC4649010, DOI: 10.1523/jneurosci.3165-15.2015.Peer-Reviewed Original ResearchMeSH KeywordsAmidinesAnalysis of VarianceAnimalsAxonsBiotinCrystallinsDextransDisease Models, AnimalFunctional LateralityGene Expression RegulationGlial Fibrillary Acidic ProteinGPI-Linked ProteinsLuminescent ProteinsMiceMice, Inbred C57BLMice, TransgenicMu-CrystallinsMyelin ProteinsNerve RegenerationNogo Receptor 1Pyramidal TractsReceptors, Cell SurfaceRecovery of FunctionSpinal Cord InjuriesConceptsCorticospinal tractCST axonsTransgenic miceMotor tractsDextran amineFunctional deficitsSpinal cordAxon regenerationSpinal Cord Injury StudySpontaneous axon regenerationSpinal cord traumaNogo receptor 1Permanent functional deficitsPersistent functional deficitsBilateral pyramidotomyDorsal hemisectionMidthoracic cordCord traumaMotor pathwaysAdult CNSCST regenerationInjury studiesLesion siteRegenerating fibersNeural repairGene-Silencing Screen for Mammalian Axon Regeneration Identifies Inpp5f (Sac2) as an Endogenous Suppressor of Repair after Spinal Cord Injury
Zou Y, Stagi M, Wang X, Yigitkanli K, Siegel CS, Nakatsu F, Cafferty WB, Strittmatter SM. Gene-Silencing Screen for Mammalian Axon Regeneration Identifies Inpp5f (Sac2) as an Endogenous Suppressor of Repair after Spinal Cord Injury. Journal Of Neuroscience 2015, 35: 10429-10439. PMID: 26203138, PMCID: PMC4510284, DOI: 10.1523/jneurosci.1718-15.2015.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsDisease Models, AnimalGene Knockdown TechniquesImmunohistochemistryInositol Polyphosphate 5-PhosphatasesMiceMice, Inbred C57BLMice, KnockoutNerve RegenerationPhosphoric Monoester HydrolasesRecovery of FunctionReverse Transcriptase Polymerase Chain ReactionSpinal Cord InjuriesConceptsSpinal cord injuryCord injuryEndogenous suppressorAxon regenerationNonoverlapping substrate specificityGenome-wide scaleHigh-throughput functional screensFunctional recoveryAxonal regenerationCNS axon repairSpinal cord injury researchDorsal hemisection injuryMammalian genesPI3K/AKT/mTOR pathwayCNS axon growthAKT/mTOR pathwayLipid phosphataseCorticospinal tract axonsCNS axon regenerationAdult mammalian CNSFunctional screenSubstrate specificityNovel suppressorShRNA resultsINPP5FPlasticity of Intact Rubral Projections Mediates Spontaneous Recovery of Function after Corticospinal Tract Injury
Siegel CS, Fink KL, Strittmatter SM, Cafferty WB. Plasticity of Intact Rubral Projections Mediates Spontaneous Recovery of Function after Corticospinal Tract Injury. Journal Of Neuroscience 2015, 35: 1443-1457. PMID: 25632122, PMCID: PMC4308593, DOI: 10.1523/jneurosci.3713-14.2015.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDesigner DrugsFunctional LateralityGene Expression RegulationGlial Fibrillary Acidic ProteinLocomotionMaleMiceMice, Inbred C57BLMice, TransgenicMuscle StrengthMyelin ProteinsNeuronal PlasticityNogo ProteinsPsychomotor DisordersPyramidal TractsRaphe NucleiRecovery of FunctionSpinal Cord InjuriesStereotyped BehaviorTime FactorsConceptsSpinal cord injurySpontaneous functional recoveryFunctional recoverySpontaneous recoveryIncomplete spinal cord injuryCorticospinal tract lesionsWeeks of lesionCorticospinal tract injuryNogo receptor 1Nucleus raphe magnusTract injuryRubrospinal projectionsTract lesionsCord injuryRaphe magnusCircuit rearrangementsAdult CNSCircuit plasticityLocomotor functionAdult micePharmacogenetic toolsRed nucleusRubral projectionReceptor 1Extensive sprouting
2014
Human NgR-Fc Decoy Protein via Lumbar Intrathecal Bolus Administration Enhances Recovery from Rat Spinal Cord Contusion
Wang X, Yigitkanli K, Kim CY, Sekine-Konno T, Wirak D, Frieden E, Bhargava A, Maynard G, Cafferty WB, Strittmatter SM. Human NgR-Fc Decoy Protein via Lumbar Intrathecal Bolus Administration Enhances Recovery from Rat Spinal Cord Contusion. Journal Of Neurotrauma 2014, 31: 1955-1966. PMID: 24964223, PMCID: PMC4245872, DOI: 10.1089/neu.2014.3355.Peer-Reviewed Original ResearchConceptsSpinal cord injuryTraumatic spinal cord injurySpinal cord contusionNeurological recoveryCord contusionRat spinal cord contusionSpinal contusion injuryLumbar intrathecal spaceLumbar spinal cordContinuous intracerebroventricular infusionRodent SCI modelsPercentage of ratsRaphespinal axonsContusion injuryAdministration regimenSCI modelContinuous infusionCord injuryIntracerebroventricular infusionIntrathecal spaceSpinal cordPreclinical modelsEffective treatmentWalking tasksClinical testingDiffusion Tensor Imaging as a Predictor of Locomotor Function after Experimental Spinal Cord Injury and Recovery
Kelley BJ, Harel NY, Kim CY, Papademetris X, Coman D, Wang X, Hasan O, Kaufman A, Globinsky R, Staib LH, Cafferty WB, Hyder F, Strittmatter SM. Diffusion Tensor Imaging as a Predictor of Locomotor Function after Experimental Spinal Cord Injury and Recovery. Journal Of Neurotrauma 2014, 31: 1362-1373. PMID: 24779685, PMCID: PMC4120934, DOI: 10.1089/neu.2013.3238.Peer-Reviewed Original ResearchConceptsSpinal cord injuryDiffusion tensor imagingCord injuryAxonal integrityLocomotor functionExperimental spinal cord injuryTraumatic spinal cord injuryFemale Sprague-Dawley ratsTensor imagingFractional anisotropyFunctional recovery assessmentSpinal cord contusionLimited functional recoveryLong-term disabilityQuantitative diffusion tensor imagingRodent SCI modelsSprague-Dawley ratsSpinal cord morphologyWhite matter pathologyCaudal spinal cordWhite matter integrityInjury epicenterMidthoracic laminectomyCord contusionPrimary outcomeNogo limits neural plasticity and recovery from injury
Schwab ME, Strittmatter SM. Nogo limits neural plasticity and recovery from injury. Current Opinion In Neurobiology 2014, 27: 53-60. PMID: 24632308, PMCID: PMC4122629, DOI: 10.1016/j.conb.2014.02.011.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCentral Nervous System DiseasesHumansMyelin ProteinsNeuronal PlasticityNogo ProteinsRecovery of FunctionSignal TransductionConceptsNeural repairCentral nervous system injuryOptic nerve injurySpinal cord traumaNervous system injuryExperience-dependent plasticityIschemic strokeNerve injuryCord traumaFunctional recoveryMultiple sclerosisSystem injuryReceptor NgR1Neural plasticityPhysiologic roleAxonal anatomyInjuryAdult mammalsMultiple studiesNogoNgR1Molecular studiesRepairSclerosisAntagonist
2012
Myelin-derived ephrinB3 restricts axonal regeneration and recovery after adult CNS injury
Duffy P, Wang X, Siegel CS, Tu N, Henkemeyer M, Cafferty WB, Strittmatter SM. Myelin-derived ephrinB3 restricts axonal regeneration and recovery after adult CNS injury. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 5063-5068. PMID: 22411787, PMCID: PMC3323955, DOI: 10.1073/pnas.1113953109.Peer-Reviewed Original ResearchConceptsAxonal regenerationAxonal growthAdult mammalian central nervous systemAdult CNS injuryDorsal hemisection injurySpinal cord injuryMammalian central nervous systemWild-type miceCentral nervous systemCaudal spinal cordAxonal guidance cuesAxonal growth inhibitionLater time pointsGreater spasticityCNS traumaHemisection injuryCrush siteOptic nerveNeurological functionCNS injuryCord injuryTransection modelGrowth restrictionSpinal cordTraumatic injury
2011
Recovery from chronic spinal cord contusion after nogo receptor intervention
Wang X, Duffy P, McGee AW, Hasan O, Gould G, Tu N, Harel NY, Huang Y, Carson RE, Weinzimmer D, Ropchan J, Benowitz LI, Cafferty WB, Strittmatter SM. Recovery from chronic spinal cord contusion after nogo receptor intervention. Annals Of Neurology 2011, 70: 805-821. PMID: 22162062, PMCID: PMC3238798, DOI: 10.1002/ana.22527.Peer-Reviewed Original ResearchConceptsChronic spinal cord injurySpinal cord injuryContusion injuryCord injurySpinal cord contusion injuryCentral nervous system injuryBresnahan locomotor scoresOpen-field BassoSpinal hemisection injuryWeight-bearing statusSpinal cord contusionMonths of treatmentNervous system injuryMyelin-derived inhibitorCaudal spinal cordPositron emission tomographyNgR1 pathwayRaphespinal axonsSpinal contusionCord contusionHemisection injuryFunctional recoveryLocomotor scoresSystem injuryControl ratsMyelin associated inhibitors: A link between injury-induced and experience-dependent plasticity
Akbik F, Cafferty WB, Strittmatter SM. Myelin associated inhibitors: A link between injury-induced and experience-dependent plasticity. Experimental Neurology 2011, 235: 43-52. PMID: 21699896, PMCID: PMC3189418, DOI: 10.1016/j.expneurol.2011.06.006.Peer-Reviewed Original ResearchConceptsExperience-dependent plasticityAnatomical rearrangementsNogo-66 receptor 1Spinal cord injuryNeurologic recoveryFunctional recoveryInciting stimulusCNS injuryCord injuryAxonal regenerationAdult CNSInjury studiesAnimal modelsReceptor 1Common receptorPaired-ImmunoglobulinMyelinInhibitorsInjuryAnatomical growthCNSReceptorsWide spectrumExtracellular matrixGrowth inhibitorInosine Augments the Effects of a Nogo Receptor Blocker and of Environmental Enrichment to Restore Skilled Forelimb Use after Stroke
Zai L, Ferrari C, Dice C, Subbaiah S, Havton LA, Coppola G, Geschwind D, Irwin N, Huebner E, Strittmatter SM, Benowitz LI. Inosine Augments the Effects of a Nogo Receptor Blocker and of Environmental Enrichment to Restore Skilled Forelimb Use after Stroke. Journal Of Neuroscience 2011, 31: 5977-5988. PMID: 21508223, PMCID: PMC3101108, DOI: 10.1523/jneurosci.4498-10.2011.Peer-Reviewed Original ResearchConceptsIntrinsic growth potentialUnilateral strokeSpinal cordLayer 5 pyramidal neuronsForelimb motor areaSimilar functional improvementEnvironmental enrichmentCause of disabilitySkilled forelimb useEffect of treatmentUndamaged cortexReceptor blockersDenervated sidePreoperative levelsNEP1-40Stroke patientsPyramidal neuronsUndamaged hemisphereSkilled reachingTreatment optionsDenervated areaIntact hemisphereReceptor antagonistClinical trialsFunctional improvement
2010
MAG and OMgp Synergize with Nogo-A to Restrict Axonal Growth and Neurological Recovery after Spinal Cord Trauma
Cafferty WB, Duffy P, Huebner E, Strittmatter SM. MAG and OMgp Synergize with Nogo-A to Restrict Axonal Growth and Neurological Recovery after Spinal Cord Trauma. Journal Of Neuroscience 2010, 30: 6825-6837. PMID: 20484625, PMCID: PMC2883258, DOI: 10.1523/jneurosci.6239-09.2010.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsBiotinCells, CulturedDextransDisease Models, AnimalFemaleFunctional LateralityGanglia, SpinalGPI-Linked ProteinsMaleMiceMice, Inbred C57BLMice, KnockoutMutationMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinNerve Tissue ProteinsNeuronsNogo ProteinsPyramidal TractsReceptors, Cell SurfaceReceptors, SerotoninRecovery of FunctionSpinal Cord InjuriesConceptsAxonal growthSpinal Cord Injury StudyMutant miceGreater axonal growthGreater behavioral recoverySpinal cord traumaWild-type miceAxonal growth inhibitionHeterozygous mutant miceDeficient myelinNeurological recoveryCNS damageTriple-mutant miceBehavioral recoveryCord traumaFunctional recoveryNeurological functionMyelin inhibitorsAxonal regrowthReceptor mechanismsInjury studiesMyelin inhibitionDecoy receptorOptimal chanceMiceCombination of NEP 1-40 Treatment and Motor Training Enhances Behavioral Recovery After a Focal Cortical Infarct in Rats
Fang PC, Barbay S, Plautz EJ, Hoover E, Strittmatter SM, Nudo RJ. Combination of NEP 1-40 Treatment and Motor Training Enhances Behavioral Recovery After a Focal Cortical Infarct in Rats. Stroke 2010, 41: 544-549. PMID: 20075346, PMCID: PMC2853474, DOI: 10.1161/strokeaha.109.572073.Peer-Reviewed Original ResearchConceptsMotor trainingWeeks postinfarctBehavioral recoverySkilled reachWeek 2Focal cortical infarctsFocal cortical ischemiaFocal ischemic infarctTreatment week 2Foot-fault testFocal ischemic injuryWeeks of treatmentSkilled reach taskNEP 1Cortical infarctsForelimb impairmentCortical ischemiaFoot faultsMotor recoveryIschemic infarctIschemic injuryMotor cortexEndothelin-1Intraventricular infusionMotor function
2009
Inosine Alters Gene Expression and Axonal Projections in Neurons Contralateral to a Cortical Infarct and Improves Skilled Use of the Impaired Limb
Zai L, Ferrari C, Subbaiah S, Havton LA, Coppola G, Strittmatter S, Irwin N, Geschwind D, Benowitz LI. Inosine Alters Gene Expression and Axonal Projections in Neurons Contralateral to a Cortical Infarct and Improves Skilled Use of the Impaired Limb. Journal Of Neuroscience 2009, 29: 8187-8197. PMID: 19553458, PMCID: PMC2856695, DOI: 10.1523/jneurosci.0414-09.2009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsBrain InfarctionCerebral CortexComplement C1qComplement C3Disease Models, AnimalExtremitiesFunctional LateralityGene Expression RegulationHeat-Shock ProteinsImmunohistochemistryInjections, IntraventricularInosineNeuronsOligonucleotide Array Sequence AnalysisProteasome Endopeptidase ComplexRatsRats, Sprague-DawleyRecovery of FunctionRNA, MessengerTreatment OutcomeUbiquitinationConceptsUndamaged neuronsSpinal cordSynaptic bouton-like structuresImpaired limbAlters gene expressionCorticospinal tract axonsSpecific cortical areasBouton-like structuresCortical infarctsCorticospinal neuronsDenervated sideUnaffected hemisphereAxon collateralsSensorimotor cortexBrain damageBrain injuryInjury modelLaser capture microdissectionAxonal projectionsGene expressionCortical areasDenervated halfComplement cascadeNeuronsAxon growthFunctional outcome is impaired following traumatic brain injury in aging Nogo-A/B-deficient mice
Marklund N, Morales D, Clausen F, Hånell A, Kiwanuka O, Pitkänen A, Gimbel DA, Philipson O, Lannfelt L, Hillered L, Strittmatter SM, McIntosh TK. Functional outcome is impaired following traumatic brain injury in aging Nogo-A/B-deficient mice. Neuroscience 2009, 163: 540-551. PMID: 19555742, PMCID: PMC2756649, DOI: 10.1016/j.neuroscience.2009.06.042.Peer-Reviewed Original ResearchConceptsTraumatic brain injuryHemispheric tissue lossNeurological motor functionWT miceBrain injuryMotor functionCortical impact (CCI) TBILittermate controlsAge-matched wild-type littermate controlsMyelin stainingTissue lossMWM taskWild-type littermate controlsCortical lesion volumeAxonal growth inhibitorsRole of NogoMyelin-derived inhibitorAbsence of NogoNeurological motorPoor prognosisFunctional outcomeHemispheric tissuePathophysiological responsesWT littermatesDeficient mice