Oligodendrocyte extracellular vesicles: a novel therapy for CNS autoimmunity

少突胶质细胞外囊泡:中枢神经系统自身免疫的新疗法

基本信息

  • 批准号:
    10115612
  • 负责人:
  • 金额:
    $ 39万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-03-01 至 2025-02-28
  • 项目状态:
    未结题

项目摘要

SUMMARY: Oligodendrocyte extracellular vesicles: a novel therapy for CNS autoimmunity. Current therapies for multiple sclerosis (MS) target the immune system in an antigen (Ag)-nonspecific manner, with potentialy serious side effects due to systemic immunosuppression. A longstanding goal in MS research is to devise an Ag-specific therapy that would suppress only harmful immune responses, while leaving the rest of the immune system intact. The prerequisite for Ag-specific therapy is identification of the target Ag. MS pathogenesis is widely believed to be driven by autoimmunity against myelin Ags. However, the relevant Ag(s) in MS remains speculative, with the possibility that these Ags differ among patients, and over time in the same patient. Numerous approaches for Ag-specific suppression of autoimmune neuroinflammation have been proven in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. These approaches rely on re- establishing peripheral tolerance for self-Ag by delivering the same self-Ag in a non-inflammatory context (eg. in PBS) via various routes, such as intravenous (i.v.), oral, or nasal. However, translation of these experimental strategies into MS therapy has been hampered by uncertainty about the relevant Ags in MS patients. In addressing this issue, we reasoned that if for tolerance induction we used oligodendrocyte (Ol)-derived extracellular vesicles (Ol-EVs), which naturally contain most or all of the myelin Ags, it would be unnecessary to identify the relevant myelin Ag(s) in each patient. Further, we also posited that i.v. injection of Ol-EVs will suppress EAE, similar to well-documented i.v. tolerance induction by free self-peptide. Indeed, our data show that Ol-EVs contained all the relevant myelin Ags and upon i.v. injection ameliorated ongoing EAE in an Ag- dependent manner, suggesting that Ol-EVs can be a universal therapeutic agent for MS. Based on these and additional preliminary data, we hypothesize that human and mouse Ol-EVs contain all relevant myelin Ags, and upon i.v. administration will ameliorate EAE induced by various myelin Ags. We additionally hypothesize that this effect is Ag-dependent and mediated by the IFN-/IL-27/PD-L1 axis. This hypothesis will be tested in the following specific aims: Aim 1. To determine the therapeutic efficacy of Ol-EVs in several EAE models. Since the significance of this project is to study Ol-EVs as a potential therapy for MS, and we do not know the relevant Ag(s) in MS, we will test the hypothesis that OL-EVs/i.v. can suppress EAE induced by any myelin Ag, because all the relevant Ags are present in OL-EVs. Aim 2. To define the mechanism of EAE suppression by Ol-EVs. Our preliminary data provide a basis for the hypothesis that Ol-EVs/i.v. induce tolerogenic APCs, which diminish pathogenic Th cell response and suppress EAE via expression of immunoregulatory molecules. Aim 3. To study the effects of human Ol-EVs in human myelin Ag-induced EAE, and in humanized mice. We will optimize production of human Ol-EVs, and test the hypothesis that human Ol-EVs/i.v. have adequate therapeutic efficacy in EAE models, and in humanized mice to determine if findings in mice are paralleled in this human-like system.
摘要:少突胶质细胞胞外囊泡:一种治疗中枢神经系统自身免疫的新方法。

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 }}

A.M. Rostami其他文献

A.M. Rostami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('A.M. Rostami', 18)}}的其他基金

ThGM Cells in CNS Autoimmunity
中枢神经系统自身免疫中的 ThGM 细胞
  • 批准号:
    10449359
  • 财政年份:
    2021
  • 资助金额:
    $ 39万
  • 项目类别:
IL-37: a novel regulator of inflammation in CNS autoimmunity
IL-37:中枢神经系统自身免疫炎症的新型调节剂
  • 批准号:
    10199564
  • 财政年份:
    2021
  • 资助金额:
    $ 39万
  • 项目类别:
ThGM Cells in CNS Autoimmunity
中枢神经系统自身免疫中的 ThGM 细胞
  • 批准号:
    10299105
  • 财政年份:
    2021
  • 资助金额:
    $ 39万
  • 项目类别:
IL-37: a novel regulator of inflammation in CNS autoimmunity
IL-37:中枢神经系统自身免疫炎症的新型调节剂
  • 批准号:
    10369694
  • 财政年份:
    2021
  • 资助金额:
    $ 39万
  • 项目类别:
Role of IL-7R in CNS autoimmunity
IL-7R 在中枢神经系统自身免疫中的作用
  • 批准号:
    10308115
  • 财政年份:
    2020
  • 资助金额:
    $ 39万
  • 项目类别:
Oligodendrocyte extracellular vesicles: a novel therapy for CNS autoimmunity
少突胶质细胞外囊泡:中枢神经系统自身免疫的新疗法
  • 批准号:
    10361415
  • 财政年份:
    2020
  • 资助金额:
    $ 39万
  • 项目类别:
Mechanisms of GM-CSF effect in CNS autoimmune demyelination
GM-CSF在中枢神经系统自身免疫性脱髓鞘中的作用机制
  • 批准号:
    10062792
  • 财政年份:
    2016
  • 资助金额:
    $ 39万
  • 项目类别:
The role of IL-27 in iv tolerance in EAE
IL-27 在 EAE 静脉注射耐受中的作用
  • 批准号:
    8897994
  • 财政年份:
    2014
  • 资助金额:
    $ 39万
  • 项目类别:
The Role of GM-CSF in the Pathogenesis of Multiple Sclerosis
GM-CSF 在多发性硬化症发病机制中的作用
  • 批准号:
    8767198
  • 财政年份:
    2014
  • 资助金额:
    $ 39万
  • 项目类别:
The Role of GM-CSF in the Pathogenesis of Multiple Sclerosis
GM-CSF 在多发性硬化症发病机制中的作用
  • 批准号:
    8911388
  • 财政年份:
    2014
  • 资助金额:
    $ 39万
  • 项目类别:

相似海外基金

Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
  • 批准号:
    495434
  • 财政年份:
    2023
  • 资助金额:
    $ 39万
  • 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
  • 批准号:
    10586596
  • 财政年份:
    2023
  • 资助金额:
    $ 39万
  • 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
  • 批准号:
    10590479
  • 财政年份:
    2023
  • 资助金额:
    $ 39万
  • 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
  • 批准号:
    10642519
  • 财政年份:
    2023
  • 资助金额:
    $ 39万
  • 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
  • 批准号:
    23K06011
  • 财政年份:
    2023
  • 资助金额:
    $ 39万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
  • 批准号:
    10682117
  • 财政年份:
    2023
  • 资助金额:
    $ 39万
  • 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
  • 批准号:
    10708517
  • 财政年份:
    2023
  • 资助金额:
    $ 39万
  • 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
  • 批准号:
    10575566
  • 财政年份:
    2023
  • 资助金额:
    $ 39万
  • 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
  • 批准号:
    23K15696
  • 财政年份:
    2023
  • 资助金额:
    $ 39万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
  • 批准号:
    23K15867
  • 财政年份:
    2023
  • 资助金额:
    $ 39万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了