2017
Disease-modifying benefit of Fyn blockade persists after washout in mouse Alzheimer's model
Smith LM, Zhu R, Strittmatter SM. Disease-modifying benefit of Fyn blockade persists after washout in mouse Alzheimer's model. Neuropharmacology 2017, 130: 54-61. PMID: 29191754, PMCID: PMC5743608, DOI: 10.1016/j.neuropharm.2017.11.042.Peer-Reviewed Original ResearchConceptsAlzheimer's modelDisease-modifying effectsDisease-modifying therapiesMouse Alzheimer’s modelsTherapy withdrawalAPPswe/Investigational agentsSynapse densityDrug washoutTransgenic modelAlzheimer's diseasePersistent benefitsPersistent improvementSaracatinibFyn inhibitorMemantineLoss of benefitDiseaseSpatial memoryMemory functionWashoutTherapySymptomsMiceWeeksConditional Deletion of Prnp Rescues Behavioral and Synaptic Deficits after Disease Onset in Transgenic Alzheimer's Disease
Salazar SV, Gallardo C, Kaufman AC, Herber CS, Haas LT, Robinson S, Manson JC, Lee MK, Strittmatter SM. Conditional Deletion of Prnp Rescues Behavioral and Synaptic Deficits after Disease Onset in Transgenic Alzheimer's Disease. Journal Of Neuroscience 2017, 37: 9207-9221. PMID: 28842420, PMCID: PMC5607466, DOI: 10.1523/jneurosci.0722-17.2017.Peer-Reviewed Original ResearchConceptsDisease onsetAlzheimer's diseaseFamilial Alzheimer's diseaseDisease pathophysiologyCellular prion proteinHippocampal synapse lossSoluble oligomeric amyloidTransgenic Alzheimer's diseaseTime of diagnosisDisease-modifying therapiesAlzheimer's disease pathophysiologyPotential therapeutic targetAD-related phenotypesMonths of ageRole of PrPSymptom onsetSynaptic deficitsPrion proteinSynapse lossCatecholaminergic neuronsPlaque densityBehavioral deficitsOligomeric amyloidMouse modelPresent symptoms
2015
A phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimer’s disease
Nygaard HB, Wagner AF, Bowen GS, Good SP, MacAvoy MG, Strittmatter KA, Kaufman AC, Rosenberg BJ, Sekine-Konno T, Varma P, Chen K, Koleske AJ, Reiman EM, Strittmatter SM, van Dyck CH. A phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimer’s disease. Alzheimer's Research & Therapy 2015, 7: 35. PMID: 25874001, PMCID: PMC4396171, DOI: 10.1186/s13195-015-0119-0.Peer-Reviewed Original ResearchRegional cerebral glucose metabolismCerebral glucose metabolismTreatment of patientsClinical efficacy measuresModerate Alzheimer's diseaseAlzheimer's diseaseEfficacy measuresGlucose metabolismCentral nervous system availabilityMultiple ascending dose studyFluorodeoxyglucose positron emission tomographyPhase IIa clinical trialMini-Mental State Examination scoreCentral nervous system penetrationPromising new therapeutic targetCSF drug levelsMultiple ascending doseOligomeric amyloid betaPhase Ib trialPlacebo-controlled trialAscending dose studyCongestive heart failureCerebrospinal fluid penetrationDisease-modifying therapiesIIa clinical trialIntravitreal Delivery of Human NgR-Fc Decoy Protein Regenerates Axons After Optic Nerve Crush and Protects Ganglion Cells in Glaucoma ModelsNgR-Fc Rescues Ganglion Cells in Glaucoma
Wang X, Lin J, Arzeno A, Choi JY, Boccio J, Frieden E, Bhargava A, Maynard G, Tsai JC, Strittmatter SM. Intravitreal Delivery of Human NgR-Fc Decoy Protein Regenerates Axons After Optic Nerve Crush and Protects Ganglion Cells in Glaucoma ModelsNgR-Fc Rescues Ganglion Cells in Glaucoma. Investigative Ophthalmology & Visual Science 2015, 56: 1357-1366. PMID: 25655801, PMCID: PMC4338631, DOI: 10.1167/iovs.14-15472.Peer-Reviewed Original ResearchConceptsOptic nerve crushFluro-GoldNerve crushAxonal regenerationGanglion cellsOptic nerve crush injuryRetinal ganglion cell degenerationRGC axonal regenerationNerve crush injuryDisease-modifying therapiesGanglion cell degenerationDecoy proteinMicrobead modelVitreal spaceIntravitreal treatmentRGC densityAxonal sproutingCrush injuryGlaucoma modelNeuroprotective effectsAnterior chamberControl ratsVision lossAnterograde labelingBolus administration