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.
目前还没有有效的治疗方法来治疗小胶质细胞病,这是一类神经退行性疾病,
是由于大脑中特殊细胞的缺失或功能失调造成的,这种细胞被称为小胶质细胞。一种潜在的治疗策略
患有小胶质细胞病的患者是用新细胞替换他们患病的小胶质细胞。NovoGlia技术
该平台使用诱导多能干细胞以高规模和高纯度产生新的小胶质细胞。
NovoGlia细胞可以安全有效地移植到年轻小鼠的大脑中,其中内源性
小胶质细胞仍在发展中,但在成人大脑中实现高水平小胶质细胞嵌合体的策略
尚未得到充分开发。本提案的目的是证明
一种新方法的可行性,该方法结合了使用商业化的
通过移植NovoGlia细胞(经工程改造可抵抗小分子药物),
抑制剂. NovoGlia开发了两种新的细胞系,这些细胞系携带突变,使其对药物产生耐药性,
在基于细胞的实验中证明了它们的活力,证实了它们的小胶质细胞转录组学特征,
在基于细胞的测定中证明了耐药性。目的1将证实在体内转录组和功能
新细胞系的保存。目标2将衡量NovoGlia细胞替代的成功,
Aim 3将优化NovoGlia细胞替代策略。成功
完成这些目标是开发新的商业治疗方法的必要的第一步
小胶质细胞病和其他潜在的神经退行性疾病。第一阶段的结果将提供证据-
支持NovoGlia治疗小胶质细胞病和其他疾病的持续开发的概念数据
神经退行性疾病
项目成果
期刊论文数量(0)
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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:














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