Stem Cell Transplantation for Neurogenetic Disease
干细胞移植治疗神经遗传性疾病
基本信息
- 批准号:8094219
- 负责人:
- 金额:$ 34.89万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-07-15 至 2013-06-30
- 项目状态:已结题
- 来源:
- 关键词:Advanced DevelopmentAffectAnimal ModelAnimalsAreaAutologousBackBeta-glucuronidaseBrainBrain DiseasesCell LineCell TransplantsCellsChildhoodDefectDiffuseDiseaseEngineeringEngraftmentEnzymesGene DeliveryGene ExpressionGenesGrantHereditary DiseaseHumanIn VitroIndividualInheritedInjection of therapeutic agentLentivirus VectorLesionLysosomal Storage DiseasesMarrowMetabolicMetabolic DiseasesModelingMorphologyMucopolysaccharidosesMucopolysaccharidosis VIIMusMutationNatureNeocortexNeuraxisNeurodegenerative DisordersNeuronsPathologicPathologyPatientsPatternPropertyProteinsRelative (related person)SafetySignal TransductionSiteSpatial DistributionStem cell transplantStromal CellsSystemTestingTimeTissuesTransplant RecipientsTransplantationTreatment EffectivenessWorkbasebrain cellbrain tissuecellular engineeringcommon treatmentexpression vectorgene therapyhuman diseasemigrationmutantnerve stem cellneurogeneticsneuropathologynovelprogenitorresearch studytherapeutic enzymetreatment strategyvector
项目摘要
DESCRIPTION (provided by applicant): Inherited metabolic disorders cause a significant number of brain diseases. A major barrier to treating such diseases is that the inherent nature of the defect results in global distribution of the pathologic lesions within the CNS. This circumstance requires that cells be corrected either throughout the CNS or in key areas where the pathologic consequences are most severe. In this grant we will investigate neural stem cell (NSC)-based approaches to treat the central nervous system (CNS) in neurogenetic disease by delivering a diffusible protein within the brain. The approach is to genetically correct the defect in NSCs in vitro and transplant the corrected cells back into the defective brain. Under the right circumstances, NSCs can migrate within the brain and differentiate into all three major lineages of brain cells. As a test system, we will use a B- glucuronidase (GUSB) deficient mouse, which is a model for human lysosomal storage diseases (LSD). There are >50 individual LSDs and they are responsible for approximately 20% of all inherited childhood genetic diseases that affect the CNS. A common treatment strategy can be used, in principle, for >90% of the LSD's. It is based on the observation that lysosomal enzymes can be secreted from genetically corrected cells, diffuse through tissue, and can be taken up by mutant cells to restore the missing enzymatic activity. Thus, delivery of the modified NSC's to only a fraction of the brain may be able to rescue a large amount of brain tissue. To achieve global delivery of the therapeutic enzyme, the transplanted cells need to be dispersed within the three dimensional space of the brain. We have demonstrated that gene therapy can work in the brains of the GUSB-deficient mice using a clonal cell line. However, there are substantial barriers to achieving permanent and complete correction, particularly in reaching the global lesions in the much larger human brain. We propose to investigate: 1) the transplantation properties and vector gene expression in primary murine NSC's as a model for autologous correction (en vivo gene therapy); 2) potential strategies to increase the migration of the NSC's away from the injection site; and 3) the effectiveness of the treatment on the neuropathology and the safety of the transplant recipients. Advances in understanding the transplantation properties of NSC's for treatment in this model should have applicability to the whole class of disease.
描述(由申请人提供):遗传性代谢紊乱导致大量脑部疾病。治疗这类疾病的主要障碍是缺陷的固有性质导致中枢神经系统内病理病变的全局分布。这种情况需要在整个中枢神经系统或病理后果最严重的关键区域对细胞进行纠正。在这项资助中,我们将研究基于神经干细胞(NSC)的方法,通过在大脑内传递扩散蛋白来治疗神经遗传性疾病的中枢神经系统(CNS)。该方法是在体外对NSCs中的缺陷进行基因校正,然后将校正后的细胞移植回有缺陷的大脑。在适当的情况下,NSCs可以在大脑内迁移并分化成所有三种主要的脑细胞谱系。作为测试系统,我们将使用B-葡萄糖醛酸酶(GUSB)缺陷小鼠,这是人类溶酶体贮积病(LSD)的模型。有50个lsd个体,大约20%的影响中枢神经系统的遗传性儿童遗传疾病是由lsd引起的。原则上,一种常见的治疗策略可以用于90%的LSD。它是基于这样的观察:溶酶体酶可以从基因校正的细胞中分泌出来,在组织中扩散,并且可以被突变细胞吸收以恢复缺失的酶活性。因此,仅将改良的NSC输送到大脑的一小部分可能就能挽救大量的脑组织。为了实现治疗酶的整体递送,移植细胞需要分散在大脑的三维空间内。我们已经证明基因治疗可以在使用克隆细胞系的gusb缺陷小鼠的大脑中起作用。然而,要实现永久和完全的矫正,特别是要达到更大的人类大脑的整体病变,存在着实质性的障碍。我们拟研究:1)将小鼠NSC的移植特性和载体基因表达作为自体校正(体内基因治疗)的模型;2)增加NSC远离注射部位迁移的潜在策略;3)治疗对神经病理的影响及移植受者的安全性。在了解NSC的移植特性以治疗该模型方面的进展应该适用于所有类型的疾病。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
JOHN H WOLFE其他文献
JOHN H WOLFE的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('JOHN H WOLFE', 18)}}的其他基金
Translational studies on cerebrospinal fluid (CSF)-directed gene therapy for global neurometabolic brain disease
脑脊液(CSF)定向基因治疗全球神经代谢性脑疾病的转化研究
- 批准号:
10379947 - 财政年份:2019
- 资助金额:
$ 34.89万 - 项目类别:
Translational studies on cerebrospinal fluid (CSF)-directed gene therapy for global neurometabolic brain disease
脑脊液(CSF)定向基因治疗全球神经代谢性脑疾病的转化研究
- 批准号:
9893931 - 财政年份:2019
- 资助金额:
$ 34.89万 - 项目类别:
Translational studies on cerebrospinal fluid (CSF)-directed gene therapy for global neurometabolic brain disease
脑脊液(CSF)定向基因治疗全球神经代谢性脑疾病的转化研究
- 批准号:
9763064 - 财政年份:2019
- 资助金额:
$ 34.89万 - 项目类别:
Translational studies on cerebrospinal fluid (CSF)-directed gene therapy for global neurometabolic brain disease
脑脊液(CSF)定向基因治疗全球神经代谢性脑疾病的转化研究
- 批准号:
10599930 - 财政年份:2019
- 资助金额:
$ 34.89万 - 项目类别:
Disseminated gene delivery to the CNS by human iPSC-derived neural stem cells
通过人类 iPSC 衍生的神经干细胞将播散性基因传递至 CNS
- 批准号:
9204865 - 财政年份:2015
- 资助金额:
$ 34.89万 - 项目类别:
Disseminated gene delivery to the CNS by human iPSC-derived neural stem cells
通过人类 iPSC 衍生的神经干细胞将播散性基因传递至 CNS
- 批准号:
8894955 - 财政年份:2015
- 资助金额:
$ 34.89万 - 项目类别:
Disseminated gene delivery to the CNS by human iPSC-derived neural stem cells
通过人类 iPSC 衍生的神经干细胞将播散性基因传递至 CNS
- 批准号:
8997131 - 财政年份:2015
- 资助金额:
$ 34.89万 - 项目类别:
Gene Transfer and NMR Studies in Alpha-Mannosidosis Brain
α-甘露糖苷沉积症脑中的基因转移和核磁共振研究
- 批准号:
8068082 - 财政年份:2010
- 资助金额:
$ 34.89万 - 项目类别:
Stem Cell Transplantation for Neurogenetic Disease
干细胞移植治疗神经遗传性疾病
- 批准号:
7459697 - 财政年份:2007
- 资助金额:
$ 34.89万 - 项目类别:
相似海外基金
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 34.89万 - 项目类别:
Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 34.89万 - 项目类别:
Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 34.89万 - 项目类别:
Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 34.89万 - 项目类别:
Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 34.89万 - 项目类别:
Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 34.89万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 34.89万 - 项目类别:
Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
- 批准号:
2301846 - 财政年份:2023
- 资助金额:
$ 34.89万 - 项目类别:
Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 34.89万 - 项目类别:
Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
- 批准号:
23K16076 - 财政年份:2023
- 资助金额:
$ 34.89万 - 项目类别:
Grant-in-Aid for Early-Career Scientists