grant
Interactions Between Diverse Brain Cell Types Drive Aicardi-Goutieres Neuropathology
Organization CHILDREN'S HOSP OF PHILADELPHIALocation PHILADELPHIA, UNITED STATESPosted 15 Aug 2024Deadline 31 Jul 2029
NIHUS FederalResearch GrantFY2025AccelerationAddressAdventitial CellAdvocacyAffectAicardi Goutieres syndromeAstrocytesAstrocytusAstrogliaAutomobile DrivingBehaviorBiologic ModelsBiological ModelsBlood - brain barrier anatomyBlood VesselsBlood-Brain BarrierBone MarrowBone Marrow Reticuloendothelial SystemBrainBrain Nervous SystemBrain VascularCD115 AntigensCNS InjuryCNS Nervous SystemCREE ENCEPHALITISCRG-2CSF-1 ReceptorCSF-1-RCSF1R Gene ProductCXCL10CXCL10 geneCalcifiedCell BodyCell Communication and SignalingCell SignalingCellsCentral Nervous SystemCerebrospinal FluidChildren's HospitalClinicalColony Stimulating Factor 1 ReceptorDNA TherapyDNA mutationDevelopmentDiseaseDisorderDouble-Stranded RNADrugsEncephalonEncephalopathiesEncephalopathy with intracranial calcification and chronic lymphocytosis of cerebrospinal fluidEncephalopathy, familial infantile, with calcification of basal ganglia and chronic cerebrospinal fluid lymphocytosisEndothelial CellsEndotheliumEnzyme GeneEnzymesGene ExpressionGene ModifiedGene TranscriptionGene Transfer ClinicalGenesGeneticGenetic ChangeGenetic InterventionGenetic TranscriptionGenetic defectGenetic mutationGenotypeHSC transplantationHemato-Encephalic BarrierHematopoietic Stem Cell TransplantHematopoietic Stem Cell TransplantationHepatitisHistopathologyHortega cellHuman GeneticsHuman PathologyIFI10IFIH1IFNINP10IP-10ImmuneImmune systemImmunesImmunologic SubtypingImmunophenotypingInflammatoryInjuryInnate Immune ResponseInterferon Induced With Helicase C Domain 1Interferon Type IInterferonsIntracellular Communication and SignalingInvestigatorsJAK kinaseJanus kinaseKnowledgeLaboratoriesLeadLymphatic cellLymphocyteLymphocyticLymphocytosisM-CSF ReceptorsMDA 5MOB-1Macrophage Colony Stimulating Factor I ReceptorMacrophage Colony-Stimulating Factor ReceptorMature LymphocyteMeasuresMediatingMedicationMiceMice MammalsMicrogliaModel SystemModelingMurineMusMutationMyelogenousMyeloidNatureNerve CellsNerve UnitNeural CellNeuraxisNeurocyteNeuronsNucleic AcidsOligodendrocytesOligodendrocytusOligodendrogliaOligodendroglia CellOutcomePathogenesisPathogenicityPathologyPathway interactionsPatientsPb elementPediatric HospitalsPericapillary CellPericytesPeripheralPeripheral Nervous SystemPerivascular CellPharmaceutical PreparationsPhenocopyPhiladelphiaPopulationProductionProto-Oncogene Protein fmsRNA EditingRNA ExpressionRNA based therapeuticsRNA based therapyRNA therapyRNA, Messenger, EditingResearch PersonnelResearchersResistanceRodent ModelRoleRouget CellsSCYB10Signal TransductionSignal Transduction SystemsSignalingSystemTestingTherapeuticTherapeutic UsesTimeTranscriptionTranslatingTransplantationUniversitiesVascular DiseasesVascular DisorderVascular EndotheliumViralWorkadenosine deaminase that acts on RNAastrocytic gliaautoinflammatoryautoinflammatory diseasesautoinflammatory disordersbiological signal transductionblood stem cell transplantationblood vessel disorderbloodbrain barrierbrain cellc-fms Proteincalcificationcell typecellular targetingcentral nervous system injurycerebral spinal fluidcerebral vascularcerebro-vascularcerebrovascularclinical translationclinically translatablecognitive disabilitycognitively disabledcombinatorialcutaneous lesionscytokinedADARdermal lesiondevelop therapydevelopmentaldouble-stranded RNA-specific adenosine deaminasedrivingdrug/agentdsRNAdsRNA adenosine deaminasedsRNA-specific adenosine deaminaseeffective therapyeffective treatmentexperienceexperimentexperimental researchexperimental studyexperimentsgIP-10gene modificationgene repair therapygene therapygene-based therapygenetic therapygenetically modifiedgenome mutationgenomic therapygitter cellheavy metal Pbheavy metal leadhematopoietic cell transplantationhematopoietic cellular transplantationhematopoietic progenitor cell transplantationinhibitorinjured CNSinjuriesinjury to the vasculatureinsightintervention developmentkinase inhibitorknock-downknockdownleukodystrophylymph cellmelanoma differentiation associated gene 5melanoma differentiation associated protein 5mesogliamicrocephaly-chorioretinopathy syndromemicroglial cellmicrogliocytemouse modelmurine modelneuro-vascular unitneurological pathologyneuronalneuropathologicneuropathologicalneuropathologyneurovascular unitnoveloverexpressoverexpressionpathwayperivascular glial cellphysical disabilityphysically disabledphysically handicappedprogramspseudotoxoplasmosis syndromeresistantskin lesionsocial rolespinal fluidsystemic inflammationsystemic inflammatory responsetargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttheoriestherapeutic RNAtherapeutic agent developmenttherapeutic developmenttherapy developmenttooltranscriptomicstransplanttreatment developmentvascularvascular dysfunctionvascular endothelial dysfunctionvascular injuryvasculopathy
Description preview
ABSTRACT
Aicardi Goutières (AGS) is a severe autoinflammatory disease that predominantly affects the brain, leading to
severe cognitive and physical disabilities. Although this disease is genetically heterogeneous, all genotypes
lead to multi-system excessive type 1 interferon (IFN) activity. How the systemic inflammatory response in AGS
leads to…
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