EVALUATION OF PROSAVIN EFFICACY TO MPTP-LESIONED MACAQUES

PROSAVIN 对 MPTP 损伤的猕猴的功效评估

基本信息

  • 批准号:
    8357571
  • 负责人:
  • 金额:
    $ 3.29万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-08-01 至 2012-04-30
  • 项目状态:
    已结题

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The use of viral vectors as carriers of therapeutic agents in the CNS is a field of great interest for the treatment of neurodegenerative diseases, most particularly for Parkinson's disease, because of the preferential loss of nigrostriatal dopaminergic neurons, and the fact that the currently used long term dopamine replacement therapy results in major side effects that considerably limit the use of such therapeutic approach in advanced patients. In the present project, Dr Smith has developed a research program supported by Oxford Biomedica in UK to determine the antiparkinsonian efficacy of a lentiviral vector transfected with the necessary enzymes and co-factor for dopamine synthesis (hereby called Prosavin), in the MPTP-treated nonhuman primate model of Parkinson's disease. A group of seven monkeys were rendered parkinsonian following chronic injections of the toxin MPTP before they received five injections of 10 microliters (ie a total of 50 microliters per structure) of the viral vector in the sensorimotor territory of the postcommissural putamen. Following the injections, animals were allowed to survive for a period of 3-6 months during which their behavior was monitored on a weekly basis to assess changes in their parkinsonian symptoms. Data obtained so far have indicated modest behavioral improvement in some, but not all monkeys that received the vector injections. Postmortem studies are in progress to assess the extent of striatal transfection and the resulting degree of striatal dopamine innervation. These findings in nonhuman primates will serve as the basic foundation for clinical trials in humans with Parkinson's disease.
这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的, 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量, 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 在CNS中使用病毒载体作为治疗剂的载体是治疗神经变性疾病,特别是帕金森病的非常感兴趣的领域,因为黑质纹状体多巴胺能神经元的优先损失,以及目前使用的长期多巴胺替代疗法导致严重副作用的事实,这大大限制了这种治疗方法在晚期患者中的使用。在本项目中,Smith博士开发了一项由英国牛津生物医学公司支持的研究计划,以确定用多巴胺合成所需的酶和辅因子转染的慢病毒载体(以下称为Prosavin)在MPTP治疗的非人灵长类帕金森病模型中的抗帕金森病疗效。一组7只猴子在慢性注射毒素MPTP后出现帕金森病,然后在连合后壳核的感觉运动区接受5次10微升(即每个结构总共50微升)的病毒载体注射。注射后,使动物存活3-6个月,在此期间每周监测其行为以评估其帕金森症状的变化。迄今为止获得的数据表明,接受载体注射的一些但不是所有猴子的行为都有适度的改善。尸检研究正在进行中,以评估纹状体转染的程度和纹状体多巴胺神经支配的程度。这些在非人灵长类动物中的发现将为帕金森病患者的临床试验奠定基础。

项目成果

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科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Yoland Smith其他文献

Yoland Smith的其他文献

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{{ truncateString('Yoland Smith', 18)}}的其他基金

Connectome of Motor Corticofugal Neurons in Parkinsonian Monkeys
帕金森猴运动皮质神经元的连接组
  • 批准号:
    10284849
  • 财政年份:
    2021
  • 资助金额:
    $ 3.29万
  • 项目类别:
Connectome of Motor Corticofugal Neurons in Parkinsonian Monkeys
帕金森猴运动皮质神经元的连接组
  • 批准号:
    10495224
  • 财政年份:
    2021
  • 资助金额:
    $ 3.29万
  • 项目类别:
Pathophysiology of the Pedunculopontine Nucleus in Parkinson's Disease
帕金森病桥脚核的病理生理学
  • 批准号:
    10213844
  • 财政年份:
    2017
  • 资助金额:
    $ 3.29万
  • 项目类别:
Pathophysiology of the Pedunculopontine Nucleus in Parkinson's Disease
帕金森病桥脚核的病理生理学
  • 批准号:
    9975917
  • 财政年份:
    2017
  • 资助金额:
    $ 3.29万
  • 项目类别:
Pathophysiology of the Pedunculopontine Nucleus in Parkinson's Disease
帕金森病桥脚核的病理生理学
  • 批准号:
    9404759
  • 财政年份:
    2017
  • 资助金额:
    $ 3.29万
  • 项目类别:
A2AR/MGLUR5 ANTAGONIST COMBINATION ANTIPARKINSONIAN THERAPY IN MPTP MONKEYS
A2AR/MGLUR5 拮抗剂联合抗帕金森病治疗 MPTP 猴
  • 批准号:
    8357543
  • 财政年份:
    2011
  • 资助金额:
    $ 3.29万
  • 项目类别:
GABA-B RECEPTORS AND PARKINSON'S DISEASE
GABA-B 受体与帕金森病
  • 批准号:
    8357385
  • 财政年份:
    2011
  • 资助金额:
    $ 3.29万
  • 项目类别:
THE THALAMOSTRIATAL SYSTEM IN PRIMATES
灵长类动物的丘脑纹状体系统
  • 批准号:
    8357447
  • 财政年份:
    2011
  • 资助金额:
    $ 3.29万
  • 项目类别:
ANATOMICAL AND PHYSIOLOGICAL CHARACTERIZATION OF THE THALAMOSTRIATAL SYSTEM
丘纹系统的解剖学和生理学特征
  • 批准号:
    8357545
  • 财政年份:
    2011
  • 资助金额:
    $ 3.29万
  • 项目类别:
BIOMARKERS FOR PRECLINICAL PARKINSON?S DISEASE
临床前帕金森病的生物标志物
  • 批准号:
    8357570
  • 财政年份:
    2011
  • 资助金额:
    $ 3.29万
  • 项目类别:

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