Therapeutic Core

治疗核心

基本信息

批准号：
8690146
负责人：
JOSEPH P STEINER
金额：
$ 45.04万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-06-16 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8690146
关键词：
AIDS clinical trial group AIDS/HIV problem Activated Lymphocyte Americas Astrocytes Biopharmaceutics Brain Clinical Cognition Disorders Development Disease Drug Kinetics Failure Functional disorder Goals HIV Highly Active Antiretroviral Therapy Hippocampus (Brain)Impaired cognition In Vitro Individual Inflammation Instruction Medical Minocycline National Institute of Mental Health Nerve Degeneration Nerve Regeneration Neurobiology Neurocognitive Neurons Neuropathogenesis Neurovirology Oxidative Stress Patients Peripheral Pharmaceutical Chemistry Phase II Clinical Trials Prevalence Property Regimen Research Research Design Research Personnel Resources System Techniques Therapeutic Therapeutic Agents Viral Viral Proteins Writing cerebral atrophy combinatorial global health high throughput screening immune activation in vitro Model in vivo in vivo Model macrophage neurogenesis neuropathology neurotoxic novel novel strategies novel therapeutic intervention novel therapeutics pre-clinical screening small molecule therapeutic development therapeutic target therapy development

项目摘要

THERAPEUTIC CORE PROJECT SUMMARY (See instructions): HIV-associated neurocognitive disorders (HAND) remain very prevalent, even among HIV-infected individuals who have been treated with highly active antiretroviral therapy. Thus, there is an unmet medical need to develop adjunctive therapies to treat HAND. Our previous studies in the Therapeutics Development core of the JHU NIMH Center for Novel Therapeutics have demonstrated that neuroprotective and/or neuroregenerative small molecule regimens protect vulnerable hippocampal and cortical neurons from oxidative stress and HIV viral proteins in vitro and in vivo, and therefore, may provide such a treatment for HAND. The continuing goal for the Therapeutics Core is to facilitate new adjunctive therapeutics development for the treatment of HIV-associated cognitive disorders. The therapeutics core will utilize techniques in neurobiology, medicinal chemistry, biopharmaceutics profiling and pharmacokinetic analysis as a combinatorial approach to identify and develop these therapies. Specifically, this Core will serve the following functions and has the following objectives: a)To use focused medium throughput screening, using in vitro models to identify novel compounds useful for treatment of HIV-associated cognitive dysfunction with the over-arching theme of reducing the sustained CNS inflammation that we believe underlies the development of HAND; b) to evaluate potential neuroprotective and neuroregenerative compounds in vivo; and c) To facilitate preclinical development of potential neuroprotective/neuroregenerative therapeutic agents, identified internally and by external investigators.

治疗核心项目摘要（请参阅说明）：即使在接受高度活性抗逆转录病毒疗法治疗的HIV感染者中，与HIV相关的神经认知障碍（手）仍然非常普遍。因此，有未满足的医疗需要开发辅助疗法来治疗手。我们先前在JHU NIMH新颖疗法中心的治疗性开发核心方面的研究表明，神经保护和/或神经加工的小分子方案可保护易感的海马和皮质神经元免受氧化应激和HIV病毒蛋白在体外和体内的治疗，因此可以提供此类处理。治疗核心的持续目标是促进与HIV相关认知障碍治疗的新的辅助治疗性开发。治疗核心将在神经生物学，药物化学，生物药物分析和药代动力学分析中利用技术来识别和开发这些疗法。具体而言，该核心将发挥以下功能并具有以下目标：a）使用聚焦的中吞吐量筛选，使用体外模型来识别可用于治疗与HIV相关的认知功能障碍的新型化合物，并以减少持续的CNS炎症为主题，我们相信我们相信这是您相信手的发展的； b）在体内评估潜在的神经保护性和神经增生化合物； c）促进潜在的神经保护/神经创新治疗的临床前开发代理商，内部和外部调查人员确定。