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

描述(由申请人提供)：SIV/Macaque研究核心将提供专业知识，以评估高效抗逆转录病毒疗法(HAART)时代的新疗法和替代标记物，在严格、有效的动物模型中，无论是否存在HAART，都能概括HIV CMS感染情况。测试的优先顺序将基于药物满足既定标准的程度。临床结果核心将是将新的治疗方法从动物模型转化为人类临床试验的关键，通过它与神经艾滋病试验财团的多重联系。SIV/Macaque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。该核心将提供以下功能：1)评估治疗开发分核心中确定的候选疗法，或由NIMH中心的研究人员或培养的原代猕猴细胞(淋巴细胞、单核/巨噬细胞、星形胶质细胞和神经前体细胞或神经前体细胞衍生的神经元)的外部研究人员确定的候选疗法，以确定是否适合在SIV猕猴模型中测试这些药物。2)提供必要的资源和专业知识，在快速、有效的SIV猕猴模型中评估体内的新型抗氧化剂/神经保护疗法，以提供体内的“概念证据”。这类研究的结果将为更大规模的猕猴研究(描述发病机制和机制，单独资助)和/或人类临床试验提供科学基础。3)与临床结果核心中心合作开发在SIV/猕猴模型中显示疗效的新疗法，以启动人类临床试验。4)与代理Marker Core合作研究新发现的HIV CNS疾病代理标志物，表征SIV/猕猴模型中该标志物的病理基础。

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.