EVALUATION OF PROSAVIN EFFICACY TO MPTP-LESIONED MACAQUES

PROSAVIN 对 MPTP 损伤的猕猴的功效评估

• 批准号: 8357571
• 负责人: Yoland Smith
• 金额: $ 3.29万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/8357571
• 关键词: Adverse effects; Animals; Antiparkinson Agents; Autopsy; Behavior; Behavioral; Chronic; Clinical Trials; Corpus striatum structure; Data; Dopamine; Enzymes; Evaluation; Foundations; Funding; Grant; Human; Injection of therapeutic agent; Lentivirus Vector; MPTP Poisoning; Macaca; Modeling; Monitor; Monkeys; National Center for Research Resources; Neurodegenerative Disorders; Parkinson Disease; Parkinsonian Disorders; Patients; Primates; Principal Investigator; Replacement Therapy; Research; Research Infrastructure; Resources; Source; Structure; Symptoms; Therapeutic; Therapeutic Agents; Toxin; Transfection; United States National Institutes of Health; Viral Vector; base; cost; dopaminergic neuron; interest; nerve supply; nonhuman primate; programs; putamen; vector

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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 在中枢神经系统中，使用病毒载体作为治疗剂的载体是一个非常感兴趣的领域，这是对神经推导性疾病的治疗，最尤其是在帕金森氏病的治疗中，由于骨膜多巴胺能神经元的优先丧失，并且当前使用长期多巴胺替补治疗的方法是限制了促成主要效果的方法，因此当前使用长期多巴胺替代的事实。在本项目中，史密斯博士开发了一项研究计划，由牛津Biomedica在英国的支持，以确定用必要的酶和多巴胺合成的必要酶和共同因素（此处称为Prosavin）转染的慢病毒载体的反帕金森氏菌功效（称为Prosavin），在MPTP培养的非人类非人类Primate Model of Parkinson's Parkinson's病中。一组七只猴子在长期注射毒素MPTP之后，在他们收到5次注射10个微量液体（即每个结构总共50微升）的病毒载体中，在后交流ptamen pitamen的感觉运动区域中注射了5份parkinsonian。注射后，允许动物生存3-6个月，在此期间，每周监测其行为，以评估其帕金森氏症状的变化。到目前为止获得的数据表明，某些但并非所有接受矢量注射的猴子的行为改善。验尸研究正在进行中，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。非人类灵长类动物中的这些发现将成为帕金森氏病人临床试验的基础基础。