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.
该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的, 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量, NCRR 赠款不直接向子项目或子项目工作人员提供资金。 使用病毒载体作为中枢神经系统中治疗剂的载体是治疗神经退行性疾病,尤其是帕金森病的一个非常令人感兴趣的领域,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,这在很大程度上限制了这种治疗方法在晚期患者中的使用。在目前的项目中,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(以下称为 Prosavin)转染的慢病毒载体在 MPTP 治疗的非人灵长类帕金森病模型中的抗帕金森病功效。一组七只猴子在长期注射毒素 MPTP 后患上帕金森病,然后在连合后壳核的感觉运动区域接受五次 10 微升(即每个结构总共 50 微升)病毒载体注射。注射后,动物可以存活 3-6 个月,在此期间每周监测它们的行为,以评估它们的帕金森症状的变化。迄今为止获得的数据表明,一些接受载体注射的猴子(但并非所有猴子)的行为有所改善。尸检研究正在进行中,以评估纹状体转染的程度以及由此产生的纹状体多巴胺神经支配程度。这些在非人类灵长类动物中的发现将成为人类帕金森病临床试验的基础。

项目成果

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专著数量(0)
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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