Gene delivery of MG53 for muscle membrane repair and functional improvement in a

MG53 的基因递送用于肌肉膜修复和功能改善

基本信息

  • 批准号:
    7909958
  • 负责人:
  • 金额:
    $ 2.79万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-03-15 至 2012-03-14
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Defects in muscle cell membrane integrity have been linked to various types of muscular dystrophies (MDs). Mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophies (DMD and BMD), while mutations in sarcoglycan (SG) genes because limb girdle muscular dystrophies (LGMDs). Today, more than 30 different genes have been identified to cause different types of MD, and they are all rare (orphan) diseases. However, the majority of MDs share similar pathological consequences from sarcolemma damage, such as elevated serum creative kinase (CK) activity, profound myofiber degeneration, and muscle wasting and weakness. Therefore, a therapeutic strategy that aims at repairing the leaky cell membranes instead of targeting each specific genetic mutation should be beneficial to many types of MD. Gene therapy targeted at muscle membrane repair and remodeling shows promise. The long- term goal is to use MG53 to restore sarcolemma integrity to any dystrophic muscle, irrespective of the hereditary or acquired origin. The immediate goal of this proposal is to determine whether systemic gene delivery of MG53 (an essential component of the membrane repair machinery) by AAV8 can render efficient in vivo initiation of sarcolemma repair, systemic rescue of skeletal muscle function, and substantial improvement of overall health in a delta-sarcoglycan-deficient Syrian hamster model, a well-established muscular dystrophy and congestive heart failure animal model. There are two specific aims: 1) to study long-term muscle membrane repair mediated by hMG53 in the TO-2 hamster model after AAV8 systemic delivery; 2) to investigate the histopathology, physiology, and whole-body functional improvement in TO-2 hamsters after AAV8-hMG53 systemic delivery. PUBLIC HEALTH RELEVANCE: The novelty of this proposal comes from the unique therapeutic concept of preventing the manifestation of muscular dystrophy by overexpressing hMG53 to restore muscle membrane integrity instead of targeting each genetic mutation responsible for causing the different types of muscular dystrophy. MG53-mediated muscle membrane repair and remodeling could clinically become an alternative therapy for any membrane leakage or disruption of muscle, including any type of muscular dystrophy and other non-genetic diseases or injuries.
描述(由申请人提供):肌肉细胞膜完整性缺陷与各种类型的肌营养不良症(MD)有关。肌营养不良蛋白基因的突变会导致Duchenne和Becker肌营养不良症(DMD和BMD),而肌聚糖(SG)基因的突变会导致肢体带状肌营养不良症(LGMD)。今天,已发现30多种不同的基因导致不同类型的MD,它们都是罕见的(孤儿)疾病。然而,大多数MD都有类似的肌膜损伤的病理后果,如血清肌酸激酶(CK)活性升高,严重的肌纤维变性,以及肌肉萎缩和无力。因此,一种旨在修复渗漏细胞膜而不是针对每个特定基因突变的治疗策略应该对多种类型的MD有利。针对肌膜修复和重塑的基因治疗显示出希望。长期目标是使用MG53来恢复任何营养不良肌肉的肌膜完整性,无论是遗传的还是后天起源的。这项建议的直接目标是确定AAV8系统地转导MG53(膜修复机制的重要组成部分)是否能够在体内有效地启动肌膜修复、全身挽救骨骼肌功能,并显著改善整体健康状况。1)研究AAV8-hMG53全身给药对TO-2仓鼠模型肌膜的长期修复作用;2)研究AAV8-hMG53全身给药对TO-2仓鼠的组织病理学、生理学及全身功能的影响。 与公共卫生相关:这项建议的新颖性来自于独特的治疗理念,即通过过表达hMG53来预防肌肉营养不良的表现,以恢复肌膜的完整性,而不是针对导致不同类型肌肉营养不良的每个基因突变。MG53介导的肌膜修复和重塑可能成为临床上治疗任何肌肉膜渗漏或破坏的替代疗法,包括任何类型的肌营养不良症和其他非遗传性疾病或损伤。

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 }}

Bo He其他文献

Bi-level programming model and hybrid genetic algorithm for flow interception problem with customer choice
双层规划模型与混合遗传算法解决客户选择截流问题
Automomous navigation based on unscented-FastSLAM using particle swarm optimization for autonomous underwater vehicles
基于使用粒子群优化的无味-FastSLAM 的自主水下航行器自主导航
  • DOI:
  • 发表时间:
    2015
  • 期刊:
  • 影响因子:
    5.6
  • 作者:
    Bo He;Lulu Ying;Shujing Zhang
  • 通讯作者:
    Shujing Zhang

Bo He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('Bo He', 18)}}的其他基金

Gene delivery of MG53 for muscle membrane repair and functional improvement in a
MG53 的基因递送用于肌肉膜修复和功能改善
  • 批准号:
    8058733
  • 财政年份:
    2010
  • 资助金额:
    $ 2.79万
  • 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:
    $ 2.79万
  • 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:
    $ 2.79万
  • 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:
    $ 2.79万
  • 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:
    $ 2.79万
  • 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:
    $ 2.79万
  • 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:
    $ 2.79万
  • 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:
    $ 2.79万
  • 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:
    $ 2.79万
  • 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:
    $ 2.79万
  • 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:
    $ 2.79万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了