Enhancing the Engraftment of Microglia for the Treatment of Neurological Disease
增强小胶质细胞的植入以治疗神经系统疾病
基本信息
- 批准号:10382086
- 负责人:
- 金额:$ 39.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-01-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAlzheimer&aposs DiseaseAnimalsBasic ScienceBiological AssayBrainCSF1R geneCell LineCell SurvivalCellsChimerismComplexCorpus striatum structureCouplesDataDevelopmentDimethyl SulfoxideDiseaseDoseDrug resistanceEngineeringEngraftmentExcisionFlow CytometryFrontotemporal DementiaGenesGenomicsHippocampus (Brain)HomeostasisHumanImmuneImmunohistochemistryIn VitroInjectionsLegal patentLicensingLipopolysaccharidesLysosomal Storage DiseasesMeasuresMicrogliaMouse Cell LineMucopolysaccharidosis IIIMusMutationNeoplasmsNeurodegenerative DisordersOralPathologyPatientsPharmaceutical PreparationsPhasePhosphorylationPlayPopulationProductionProsencephalonReceptor SignalingResearchResistanceRoleSalineSupportive careTechnologyTherapeuticTissuesTransplantationTyrosineUrsidae FamilyWorkbasebrain cellbrain tissuecellular engineeringdensitydrug discoveryeffective therapyexperimental studyfrontal lobegenetically modified cellshuman pluripotent stem cellin vivoinduced pluripotent stem cellinhibitorloss of functionnervous system disordernovelnovel strategiesnovel therapeuticspathogenpostnatalpreclinical safetyprecursor cellpreservationresponse to injurysmall molecule inhibitorstandard of caresuccesstranscriptometranscriptomicstreatment strategy
项目摘要
There are no effective treatments for microgliopathies, a class of neurodegenerative disorders that are caused
by the absence or misfunction of specialized cells in the brain, called microglia. One potential strategy to treat
patients with a microgliopathy is to replace their diseased microglia with new cells. The NovoGlia technology
platform uses induced pluripotent stem cells to generate new microglia cells at high scale and with high purity.
NovoGlia cells can be safely and effectively transplanted into the brains of young mice, in which endogenous
microglia are still developing, yet strategies that enable high levels of microglial chimerism within adult brains
with a fully occupied niche have yet to be developed. The objective of this proposal is to demonstrate the
feasibility of a novel approach that combines the depletion of endogenous microglia using a commercially
available drug with the transplantation of NovoGlia cells that are engineered to be resistant to the small molecule
inhibitor. NovoGlia developed two novel cell lines that bear mutations making them resistant to the drug, and
demonstrated their viability in cell-based experiments, confirmed their microglia transcriptomic profile, and
demonstrated drug resistance in cell-based assay. Aim 1 will confirm the in vivo transcriptomic and functional
preservation of the novel cell lines. Aim 2 will measure the success NovoGlia cell replacement in the presence
of variable doses of inhibitor in vivo, and Aim 3 will optimize the NovoGlia cell replacement strategy. Successful
completion of these Aims is a necessary first step in developing new commercial therapeutics for the treatment
of microgliopathies and potentially other neurodegenerative diseases. Phase I results will provide proof-of-
concept data to support the continued development of NovoGlia therapies for microgliopathies and other
neurodegenerative diseases.
小神经胶质病是一种神经退行性疾病,目前尚无有效的治疗方法
项目成果
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Sunil Gandhi其他文献
Sunil Gandhi的其他文献
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{{ truncateString('Sunil Gandhi', 18)}}的其他基金
Development of a stem cell platform for the treatment of neurodegenerativemicrogliopathies
开发用于治疗神经退行性小胶质细胞病的干细胞平台
- 批准号:
10323423 - 财政年份:2021
- 资助金额:
$ 39.99万 - 项目类别:
Reorganization of the Central Visual System by Inhibitory Neuron Transplantation
通过抑制性神经元移植重组中枢视觉系统
- 批准号:
9919570 - 财政年份:2019
- 资助金额:
$ 39.99万 - 项目类别:
Rewiring cortex using inhibitory neuron transplantation
使用抑制性神经元移植重新连接皮质
- 批准号:
8571570 - 财政年份:2013
- 资助金额:
$ 39.99万 - 项目类别:
2-Photon Imaging of synaptic remodeling in visual cortex
视觉皮层突触重塑的 2 光子成像
- 批准号:
7195002 - 财政年份:2005
- 资助金额:
$ 39.99万 - 项目类别:
2-Photon Imaging of synaptic remodeling in visual cortex
视觉皮层突触重塑的 2 光子成像
- 批准号:
7007311 - 财政年份:2005
- 资助金额:
$ 39.99万 - 项目类别: