Center for Novel Therapeutics for HIV Associated Cognitive Disorders-Animal Core

描述（由申请人提供）：SIV/猕猴研究中心将提供专业知识，以在一个严格的、经验证的动物模型中评估高效抗逆转录病毒治疗（HAART）时代的新型治疗剂和替代标志物，该模型在不存在或存在HAART的情况下重现HIV CMS感染。测试的优先顺序将基于药物符合既定标准的程度。临床结果核心将是至关重要的，通过它与神经艾滋病试验联盟的多重连接，将新的治疗方法从动物模型转化为人类临床试验。SIV/猕猴研究核心将在目前的JHU NIMH中心发挥核心作用，并将与许多其他核心互动。本核心将发挥以下功能：1）评价治疗开发子核心中或NIMH中心研究者或外部研究者在培养的原代猕猴细胞（淋巴细胞、单核细胞/巨噬细胞、星形胶质细胞和神经祖细胞或神经祖细胞衍生的神经元）中确定的候选治疗药物，以确定是否适合在SIV猕猴模型中检测药物。2)提供必要的资源和专业知识，以在快速、经验证的SIV猕猴模型中评价体内新型抗氧化剂/神经保护疗法，以提供体内“概念验证”。这些研究的结果将为在猕猴中进行的更大规模的研究（以描述发病机制和机制，单独资助）和/或人体临床试验提供科学依据。3)与临床结果核心合作，研究在SIV/猕猴模型中显示有效性的新疗法，以启动人体临床试验。4)与替代标志物核心合作，研究新发现的HIV CNS疾病的替代标志物，表征SIV/猕猴模型中标志物的病理基础。

DESCRIPTION (provided by applicant): The SIV/Macaque Research Core will provide the expertise to evaluate novel therapeutics and surrogate markers in the era of highly active antiretroviral therapy (HAART) in a rigorous, validated animal model that recapitulates HIV CMS infection either in the absence or presence of HAART. Priority for testing will be based on how well the drug meets the established criteria. The Clinical Outcomes Core will be essential to translate novel therapeutics from the animal model into human clinical trials through it multiple connections to the Neuro-AIDS trial consortia. The SIV/Macaque Research Core will play a central role in the current JHU NIMH Center, and will interact with many of the other Cores. This Core will serve the following functions: 1) To evaluate candidate therapeutics identified in the Therapeutic Development Sub-Core or by investigators in the NIMH Center or external investigators in cultured primary macaque cells (lymphocytes, monocyte/macrophages, astrocytes and neural progenitor cells or neuroprogenitor-derived neurons) to determine whether it is appropriate to test the drugs in the SIV macaque model. 2) To provide the resources and expertise necessary to evaluate novel antioxidant/neuroprotective therapeutics in vivo in a rapid, validated SIV macaque model to provide "proof of concept" in vivo. The results of such studies will provide the scientific basis for larger studies in macaques (to delineate pathogenesis and mechanism, funded separately) and/or human clinical trials. 3) To collaborate with the Clinical Outcomes Core on novel therapeutics that show efficacy in the SIV/macaque model to initiate human clinical trials. 4) To collaborate with the Surrogate Marker Core on newly identified surrogate markers for HIV CNS disease, characterizing the pathological basis for the marker in the SIV/macaque model.