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
Molecular and cellular evolution of the primate dorsolateral prefrontal cortex
Ma S, Skarica M, Li Q, Xu C, Risgaard RD, Tebbenkamp ATN, Mato-Blanco X, Kovner R, Krsnik Ž, de Martin X, Luria V, Martí-Pérez X, Liang D, Karger A, Schmidt DK, Gomez-Sanchez Z, Qi C, Gobeske KT, Pochareddy S, Debnath A, Hottman CJ, Spurrier J, Teo L, Boghdadi AG, Homman-Ludiye J, Ely JJ, Daadi EW, Mi D, Daadi M, Marín O, Hof PR, Rasin MR, Bourne J, Sherwood CC, Santpere G, Girgenti MJ, Strittmatter SM, Sousa AMM, Sestan N. Molecular and cellular evolution of the primate dorsolateral prefrontal cortex. Science 2022, 377: eabo7257. PMID: 36007006, PMCID: PMC9614553, DOI: 10.1126/science.abo7257.Peer-Reviewed Original ResearchConceptsMolecular differencesSingle-nucleus transcriptomesSubset of speciesNeuropsychiatric risk genesCellular evolutionCellular repertoireEvolutionary specializationDorsolateral prefrontal cortexRate-limiting enzymeDivergent featuresRisk genesAnthropoid primatesPrefrontal cortexPrimate dorsolateral prefrontal cortexCertain interneuronsNeuropeptide somatostatinDopamine productionGranular neuronsTyrosine hydroxylaseCell subtypesExpressionTranscriptomeAdult humansGenesPrimates
2019
Limiting Neuronal Nogo Receptor 1 Signaling during Experimental Autoimmune Encephalomyelitis Preserves Axonal Transport and Abrogates Inflammatory Demyelination
Lee JY, Kim MJ, Thomas S, Oorschot V, Ramm G, Aui PM, Sekine Y, Deliyanti D, Wilkinson-Berka J, Niego B, Harvey AR, Theotokis P, McLean C, Strittmatter SM, Petratos S. Limiting Neuronal Nogo Receptor 1 Signaling during Experimental Autoimmune Encephalomyelitis Preserves Axonal Transport and Abrogates Inflammatory Demyelination. Journal Of Neuroscience 2019, 39: 5562-5580. PMID: 31061088, PMCID: PMC6616297, DOI: 10.1523/jneurosci.1760-18.2019.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAxonal TransportAxonsCells, CulturedEncephalomyelitis, Autoimmune, ExperimentalFemaleHumansIntercellular Signaling Peptides and ProteinsKinesinsMaleMiceMice, Inbred C57BLMiddle AgedMyelin SheathNerve Tissue ProteinsNogo Receptor 1Retinal Ganglion CellsSignal TransductionConceptsExperimental autoimmune encephalomyelitisCollapsin response mediator protein 2Optic nerveAxonal degenerationMultiple sclerosisAxonal vesicular transportAutoimmune encephalomyelitisInflammatory demyelinationAxonal integritySeverity of EAECre deletionAxonal transportRetinal ganglion cell axonsAxonal motor proteinsEAE-induced miceImmune-mediated destructionProgressive multiple sclerosisNeuron-specific deletionNogo receptor 1Ganglion cell axonsAnterograde transportFlx/Response mediator protein 2Adeno-associated virus serotype 2Phosphorylation of CRMP2
2016
SCISSOR—Spinal Cord Injury Study on Small molecule-derived Rho inhibition: a clinical study protocol
Kopp MA, Liebscher T, Watzlawick R, Martus P, Laufer S, Blex C, Schindler R, Jungehulsing GJ, Knüppel S, Kreutzträger M, Ekkernkamp A, Dirnagl U, Strittmatter SM, Niedeggen A, Schwab JM. SCISSOR—Spinal Cord Injury Study on Small molecule-derived Rho inhibition: a clinical study protocol. BMJ Open 2016, 6: e010651. PMID: 27466236, PMCID: PMC4964175, DOI: 10.1136/bmjopen-2015-010651.Peer-Reviewed Original ResearchConceptsSpinal cord injurySystemic inflammatory response syndromeNeuropathic painHeterotopic ossificationMotor complete spinal cord injuryPrimary safety end pointEnd pointOpen-label pilot trialImproved motor recoveryPrimary safety analysisSafety end pointSecondary end pointsSerious adverse eventsSevere gastrointestinal bleedingInflammatory response syndromeSecondary outcome assessmentsWarrants clinical investigationAnti-inflammatory drugsClinical study protocolClinical trial protocolGood clinical practiceRho inhibitionDeclaration of HelsinkiGastroduodenal bleedingGastrointestinal bleeding
2012
Limiting multiple sclerosis related axonopathy by blocking Nogo receptor and CRMP-2 phosphorylation
Petratos S, Ozturk E, Azari MF, Kenny R, Lee JY, Magee KA, Harvey AR, McDonald C, Taghian K, Moussa L, Aui P, Siatskas C, Litwak S, Fehlings MG, Strittmatter SM, Bernard CC. Limiting multiple sclerosis related axonopathy by blocking Nogo receptor and CRMP-2 phosphorylation. Brain 2012, 135: 1794-1818. PMID: 22544872, PMCID: PMC3589918, DOI: 10.1093/brain/aws100.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnalysis of VarianceAnimalsAntibodiesAxonsCD3 ComplexCell Line, TumorDemyelinating DiseasesDisease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalFemaleGene Expression RegulationGlycoproteinsGPI-Linked ProteinsGreen Fluorescent ProteinsHumansImmunoprecipitationIntercellular Signaling Peptides and ProteinsMaleMiceMice, Inbred C57BLMice, KnockoutMiddle AgedMultiple SclerosisMutationMyelin ProteinsMyelin-Oligodendrocyte GlycoproteinNerve DegenerationNerve Tissue ProteinsNeuroblastomaNeurofilament ProteinsNogo Receptor 1Optic NervePeptide FragmentsPhosphorylationReceptors, Cell SurfaceRetinal Ganglion CellsSeverity of Illness IndexSilver StainingSpinal CordTau ProteinsTime FactorsTransduction, GeneticTubulinConceptsExperimental autoimmune encephalomyelitisAutoimmune encephalomyelitisMyelin oligodendrocyte glycoproteinMultiple sclerosisAxonal degenerationSpinal cordChronic active multiple sclerosis lesionsOptic nerve axonal degenerationNogo-66 receptor 1CRMP-2Axonal growth inhibitorsCollapsin response mediator protein 2Improved clinical outcomesSpinal cord neuronsRetinal ganglion cellsResponse mediator protein 2Central nervous systemViable therapeutic targetAdeno-associated viral vectorMultiple sclerosis lesionsClinical outcomesOptic nerveCord neuronsOligodendrocyte glycoproteinGanglion cells
1986
Parkinson's disease: Nigral receptor changes support peptidergic role in nigrostriatal modulation
Uhl G, Hackney G, Torchia M, Stranov V, Tourtellotte W, Whitehouse P, Tran V, Strittmatter S. Parkinson's disease: Nigral receptor changes support peptidergic role in nigrostriatal modulation. Annals Of Neurology 1986, 20: 194-203. PMID: 3019228, DOI: 10.1002/ana.410200204.Peer-Reviewed Original ResearchConceptsKappa-opiate receptorsIdiopathic Parkinson's diseaseNormal human brainNigrostriatal circuitryPeptidergic influencesReceptor changesSubstantia nigraMore modest reductionsSerotonin receptorsParkinson's diseaseBenzodiazepine receptorsAutoradiographic studyModest reductionReceptorsAngiotensinSomatostatinHuman brainDiseaseDopamineBenzodiazepines IPatientsNeurotensinSubtypesBrainNigra