2023
Soluble Nogo-Receptor-Fc decoy (AXER-204) in patients with chronic cervical spinal cord injury in the USA: a first-in-human and randomised clinical trial
Maynard G, Kannan R, Liu J, Wang W, Lam T, Wang X, Adamson C, Hackett C, Schwab J, Liu C, Leslie D, Chen D, Marino R, Zafonte R, Flanders A, Block G, Smith E, Strittmatter S. Soluble Nogo-Receptor-Fc decoy (AXER-204) in patients with chronic cervical spinal cord injury in the USA: a first-in-human and randomised clinical trial. The Lancet Neurology 2023, 22: 672-684. PMID: 37479373, PMCID: PMC10410101, DOI: 10.1016/s1474-4422(23)00215-6.Peer-Reviewed Original ResearchConceptsUpper extremity motor scoreSpinal cord injuryChronic spinal cord injuryTreatment-related adverse eventsAdverse eventsDay 169Intrathecal dosesCord injuryClinical trialsAmerican Spinal Injury Association Impairment Scale (AIS) gradeCervical traumatic spinal cord injuryChronic cervical spinal cord injuryCommon treatment-related adverse eventsCervical spinal cord injurySevere spinal cord injuryTraumatic spinal cord injuryPost-hoc subgroup analysesPersistent neurological deficitsDouble-blind comparisonKey secondary objectiveNational InstituteOpen labelAdvancing Translational SciencesPlacebo groupNeurological deficits
2022
Rabphilin3A reduces integrin-dependent growth cone signaling to restrict axon regeneration after trauma
Sekine Y, Kannan R, Wang X, Strittmatter SM. Rabphilin3A reduces integrin-dependent growth cone signaling to restrict axon regeneration after trauma. Experimental Neurology 2022, 353: 114070. PMID: 35398339, PMCID: PMC9555232, DOI: 10.1016/j.expneurol.2022.114070.Peer-Reviewed Original ResearchConceptsAxon regenerationModerate spinal cord contusion injurySpinal cord contusion injuryTraumatic spinal cord injuryAdult mammalian central nervous systemGrowth conesRetinal ganglion cell axonsOptic nerve crushSpinal cord crush injuryGanglion cell axonsSpinal cord injuryMammalian central nervous systemCentral nervous systemCorticospinal axon regenerationContusion injuryAxonal sproutingCrush injuryNerve crushAxonal growth conesCord injuryAxon sproutingCell axonsProximal bodyNervous systemNeural repairTranslational PET Imaging of Spinal Cord Injury with the Serotonin Transporter Tracer [11C]AFM
Fang H, Rossano S, Wang X, Nabulsi N, Kelley B, Fowles K, Ropchan J, Strittmatter SM, Carson RE, Huang Y. Translational PET Imaging of Spinal Cord Injury with the Serotonin Transporter Tracer [11C]AFM. Molecular Imaging And Biology 2022, 24: 560-569. PMID: 35020138, PMCID: PMC9550197, DOI: 10.1007/s11307-021-01698-7.Peer-Reviewed Original ResearchConceptsSpinal cord injurySpinal cordHealthy ratsHuman spinal cordCord injurySerotonin transporterRat modelRodent modelsPET imagingTranslational PET imagingSCI rat modelIntact spinal cordSpinal cord caudalRodent spinal cordSerotonin transporter tracerUse of PETCervical uptakeSERT changesSCI animalsSCI patientsPresynaptic serotonin transporterCord caudalAxon damageSerotonin systemSERT radioligand
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
2018
Diltiazem Promotes Regenerative Axon Growth
Huebner EA, Budel S, Jiang Z, Omura T, Ho TS, Barrett L, Merkel JS, Pereira LM, Andrews NA, Wang X, Singh B, Kapur K, Costigan M, Strittmatter SM, Woolf CJ. Diltiazem Promotes Regenerative Axon Growth. Molecular Neurobiology 2018, 56: 3948-3957. PMID: 30232777, PMCID: PMC6424671, DOI: 10.1007/s12035-018-1349-5.Peer-Reviewed Original ResearchConceptsL-type calcium channel blockerDorsal root gangliaCentral nervous systemChondroitin sulfate proteoglycanAxon regenerationMouse dorsal root gangliaAdult central nervous systemHuman sensory neuronsCalcium channel blockersSpinal cord injuryRat cortical culturesCord injuryAxonal regrowthRoot gangliaCortical culturesChannel blockersRegenerative propensityRegenerative axon growthSensory neuronsNervous systemPharmacological enhancersAxon growthPermanent lossSulfate proteoglycanAxotomyThe nociceptin receptor inhibits axonal regeneration and recovery from spinal cord injury
Sekine Y, Siegel CS, Sekine-Konno T, Cafferty WBJ, Strittmatter SM. The nociceptin receptor inhibits axonal regeneration and recovery from spinal cord injury. Science Signaling 2018, 11 PMID: 29615517, PMCID: PMC6179440, DOI: 10.1126/scisignal.aao4180.Peer-Reviewed Original ResearchConceptsSpinal cord injuryCord injuryAxonal regenerationMid-thoracic spinal cordTraumatic spinal cord injuryPartial neurological recoveryTraumatic CNS injuryDorsal hemisectionNeurological recoveryPeptide nociceptinCNS injuryAxon sproutingORL1 agonistSelective blockadeSpinal cordLocomotor functionNociceptin receptorAxon regenerationNeural repairPrimary neuronsNgR1 proteinAxonal growthNull miceMRNA expressionORL1
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 overexpressionCrushInhibitorsIdentification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury
Fink KL, López-Giráldez F, Kim IJ, Strittmatter SM, Cafferty WB. Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury. Cell Reports 2017, 18: 2687-2701. PMID: 28297672, PMCID: PMC5389739, DOI: 10.1016/j.celrep.2017.02.058.Peer-Reviewed Original ResearchConceptsSpinal cord injuryCentral nervous systemFunctional recoveryIntact neuronsAdult mammalian central nervous systemPartial spinal cord injuryInjury-induced sproutingUnilateral brainstem lesionsGreater functional recoverySpontaneous functional recoveryCorticospinal motor neuronsCorticospinal tract axonsMammalian central nervous systemWild-type miceNew synapse formationGrowth modulatorsAdjacent injuryBrainstem lesionsCord injuryFunctional deficitsIntact circuitryCNS neuronsMotor neuronsCircuit plasticityNervous system
2016
Rewiring the spinal cord: Direct and indirect strategies
Dell’Anno M, Strittmatter SM. Rewiring the spinal cord: Direct and indirect strategies. Neuroscience Letters 2016, 652: 25-34. PMID: 28007647, PMCID: PMC5466898, DOI: 10.1016/j.neulet.2016.12.002.Peer-Reviewed Original ResearchConceptsSpinal cordNeural stem cellsNeural stem cell-derived neuronsTransplanted neural stem cellsNeural stem cell transplantationAdult central nervous systemLong-distance axonsNeutralization of myelinRecipient spinal cordStem cell transplantationSpinal cord injuryStem cell-derived neuronsCentral nervous systemCell-derived neuronsIntrinsic regenerative capacityPoor intrinsic regenerative capacityStem cellsNeurologic recoveryAxonal sproutingSecondary complicationsCell transplantationCord injuryAxonal regenerationGlial cellsAdult brain
2015
Gene-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 outcome
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 injurySmall-molecule-induced Rho-inhibition: NSAIDs after spinal cord injury
Kopp MA, Liebscher T, Niedeggen A, Laufer S, Brommer B, Jungehulsing GJ, Strittmatter SM, Dirnagl U, Schwab JM. Small-molecule-induced Rho-inhibition: NSAIDs after spinal cord injury. Cell And Tissue Research 2012, 349: 119-132. PMID: 22350947, PMCID: PMC3744771, DOI: 10.1007/s00441-012-1334-7.Peer-Reviewed Original ResearchConceptsSpinal cord injuryCentral nervous systemAxonal plasticityCord injuryAcute spinal cord injuryExperimental spinal cord injuryNon-steroid anti-inflammatory drugsRelevant SCI modelGrowth-inhibitory environmentCNS injury modelsAnti-inflammatory drugsOligodendrocyte myelin glycoproteinRhoA inhibitionRepulsive guidance moleculeMotor recoveryAxonal sproutingPreclinical evidenceFunctional recoveryLocomotor recoverySCI modelChondroitin sulfate proteoglycanCNS injuryNeurofunctional outcomeGrowth cone collapsePossible clinical translation
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 inhibitor
2010
Nogo Receptor Deletion and Multimodal Exercise Improve Distinct Aspects of Recovery in Cervical Spinal Cord Injury
Harel NY, Song KH, Tang X, Strittmatter SM. Nogo Receptor Deletion and Multimodal Exercise Improve Distinct Aspects of Recovery in Cervical Spinal Cord Injury. Journal Of Neurotrauma 2010, 27: 2055-2066. PMID: 20809785, PMCID: PMC2978056, DOI: 10.1089/neu.2010.1491.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalExercise TherapyFemaleGene DeletionGenotypeGPI-Linked ProteinsHand StrengthImmunohistochemistryMaleMiceMice, Inbred C57BLMyelin ProteinsNeuronal PlasticityNogo Receptor 1Physical Conditioning, AnimalPostural BalanceReceptors, Cell SurfaceReproducibility of ResultsSerotoninSpinal CordSpinal Cord InjuriesWalkingConceptsSpinal cord injuryCord injuryCervical spinal cord injuryIncomplete spinal cord injuryCervical spinal injurySignificant histological differencesMultimodal exerciseExercise trainingLateral hemisectionReceptor deletionSpinal injuryLesion modelMouse modelAdult miceLesion sizeGene deletionHistological differencesNeural plasticityMild deficitsHistological analysisTraining regimenInjuryPhysical interventionsC3-C4MiceGenetic Deletion and Pharmacological Inhibition of Nogo-66 Receptor Impairs Cognitive Outcome after Traumatic Brain Injury in Mice
Hånell A, Clausen F, Björk M, Jansson K, Philipson O, Nilsson LN, Hillered L, Weinreb PH, Lee D, McIntosh TK, Gimbel DA, Strittmatter SM, Marklund N. Genetic Deletion and Pharmacological Inhibition of Nogo-66 Receptor Impairs Cognitive Outcome after Traumatic Brain Injury in Mice. Journal Of Neurotrauma 2010, 27: 1297-1309. PMID: 20486800, PMCID: PMC2942864, DOI: 10.1089/neu.2009.1255.Peer-Reviewed Original ResearchConceptsTraumatic brain injuryMossy fiber sproutingSoluble NgR1Fiber sproutingBrain injuryCortical impact injury modelEarly post-injury periodNogo-66 receptor 1Hippocampal mossy fiber sproutingBehavioral recovery processSham-injured animalsBrain-injured animalsPost-injury periodSpinal cord injuryOligodendrocyte myelin glycoproteinPharmacological neutralizationBehavioral recoveryFunctional recoveryLoss of tissueCord injuryTimm stainInjury modelMotor functionRodent modelsHistological effects
2009
Rho-Associated Kinase II (ROCKII) Limits Axonal Growth after Trauma within the Adult Mouse Spinal Cord
Duffy P, Schmandke A, Schmandke A, Sigworth J, Narumiya S, Cafferty WB, Strittmatter SM. Rho-Associated Kinase II (ROCKII) Limits Axonal Growth after Trauma within the Adult Mouse Spinal Cord. Journal Of Neuroscience 2009, 29: 15266-15276. PMID: 19955379, PMCID: PMC2855556, DOI: 10.1523/jneurosci.4650-09.2009.Peer-Reviewed Original ResearchMeSH KeywordsAmidesAnalysis of VarianceAnimalsAxonsBehavior, AnimalBrain InjuriesCA1 Region, HippocampalCells, CulturedCholera ToxinEnzyme InhibitorsGanglia, SpinalGene Expression RegulationMedian NeuropathyMiceMice, Inbred C57BLMice, KnockoutMyelin ProteinsNerve RegenerationNeuronsNogo ProteinsPyridinesReceptors, Calcitonin Gene-Related PeptideRhizotomyRho-Associated KinasesSpinal Cord InjuriesTime FactorsVersicansConceptsSpinal cordCNS traumaFunctional recoveryBasso Mouse Scale scoresSpinal Cord Injury StudyAxonal growthDorsal root entry zoneDorsal root ganglion neuronsAdult mouse spinal cordAxonal growth inhibitorsSpinal cord hemisectionRoot entry zoneSpinal cord injuryCaudal spinal cordMouse spinal cordDorsal hemisectionRaphespinal axonsDorsal rhizotomyCrush injuryCord hemisectionCorticospinal axonsChondroitin sulfate proteoglycanCord injuryGanglion neuronsInjury paradigms