Intracellular mitochondrial enzyme replacement therapy for heart and skeletalmyopathy in Barth Syndrome

细胞内线粒体酶替代疗法治疗巴特综合征的心脏和骨骼肌病

基本信息

  • 批准号:
    9546783
  • 负责人:
  • 金额:
    $ 33.69万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-08-01 至 2020-08-31
  • 项目状态:
    已结题

项目摘要

Abstract: Intracellular mitochondrial enzyme replacement therapy for heart and skeletal myopathy in Barth Syndrome Barth Syndrome is an X-linked disorder resulting from defects in the gene encoding Tafazzin, an acyltransferase that modifies cardiolipin to the tetralinoleoyl form and is essential for mitochondrial respiration. The clinical manifestations of Barth Syndrome include muscular hypotonia, cardiomyopathy and neutropenia. At present, no effective therapy exists for affected individuals. The main issue that this project will address is whether an enzyme replacement strategy in which recombinant tafazzin is linked to a cellular penetrating peptide can promote uptake into tafazzin- deficient cells, restore cardiolipin remodeling, suppress abnormal production of mitochondrial reactive oxygen species (ROS), restore normal mitochondrial respiration, improve heart and skeletal muscle performance and improve neutropenia. This project will utilize a mouse model of Barth Syndrome from Jackson laboratories and initial studies to characterize baseline function in heart and skeletal muscle have been done. Other significant milestones include generation and purification of recombinant tafazzin protein that has been modified to contain a cellular permeability peptide, along with verification of its ability to enter cells and correct both cardiopin remodeling and mitochondrial respiration defects in vitro and in live animals. Other project findings are that tafazzin-deficient myocytes produce ROS at higher levels than control cells, and that exogenous tafazzin protein suppresses this excess ROS generation. In this proposal, elucidation of mechanisms by which recombinant tafazzin engineered for intracellular uptake can enter cells and correct the metabolic defects in tafazzin-deficient cells or animals will facilitate understanding of whether this novel recombinant tafazzin reagent can provide a treatment for cardiomyopathy, skeletal myopathy and neutropenia in Barth Syndrome patients.
摘要:细胞内线粒体酶替代治疗心脏和骨骼

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(1)

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MICHAEL T CHIN其他文献

MICHAEL T CHIN的其他文献

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{{ truncateString('MICHAEL T CHIN', 18)}}的其他基金

Medical Scientist Training Program at Tufts University
塔夫茨大学医学科学家培训项目
  • 批准号:
    10626366
  • 财政年份:
    2023
  • 资助金额:
    $ 33.69万
  • 项目类别:
Functional assay development for tafazzin enzyme replacement candidate selection
用于 tafazzin 酶替代候选选择的功能测定开发
  • 批准号:
    10722856
  • 财政年份:
    2021
  • 资助金额:
    $ 33.69万
  • 项目类别:
Functional assay development for tafazzin enzyme replacement candidate selection
用于 tafazzin 酶替代候选选择的功能测定开发
  • 批准号:
    10405485
  • 财政年份:
    2021
  • 资助金额:
    $ 33.69万
  • 项目类别:
Functional assay development for tafazzin enzyme replacement candidate selection
用于 tafazzin 酶替代候选选择的功能测定开发
  • 批准号:
    10213565
  • 财政年份:
    2021
  • 资助金额:
    $ 33.69万
  • 项目类别:
In utero and early life diesel exposure, epigenetic modification and heart failur
子宫内和生命早期柴油暴露、表观遗传修饰和心力衰竭
  • 批准号:
    8899545
  • 财政年份:
    2014
  • 资助金额:
    $ 33.69万
  • 项目类别:
In utero and early life diesel exposure, epigenetic modification and heart failur
子宫内和生命早期柴油暴露、表观遗传修饰和心力衰竭
  • 批准号:
    8771328
  • 财政年份:
    2014
  • 资助金额:
    $ 33.69万
  • 项目类别:
Project 4: Myocardial Inury and Apoptosis with DE Exposure
项目 4:DE 暴露引起的心肌损伤和细胞凋亡
  • 批准号:
    8278532
  • 财政年份:
    2011
  • 资助金额:
    $ 33.69万
  • 项目类别:
Role of CHF1/Hey2 in Hypertrophy and Heart Failure
CHF1/Hey2 在肥厚和心力衰竭中的作用
  • 批准号:
    7597233
  • 财政年份:
    2006
  • 资助金额:
    $ 33.69万
  • 项目类别:
Role of CHF1/Hey2 in Hypertrophy and Heart Failure
CHF1/Hey2 在肥厚和心力衰竭中的作用
  • 批准号:
    7320073
  • 财政年份:
    2006
  • 资助金额:
    $ 33.69万
  • 项目类别:
Role of CHF1/Hey2 in Hypertrophy and Heart Failure
CHF1/Hey2 在肥厚和心力衰竭中的作用
  • 批准号:
    7216341
  • 财政年份:
    2006
  • 资助金额:
    $ 33.69万
  • 项目类别:

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Hedgehog酰基转移酶化学探针的设计
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