Pilot Proteomics Center for HIV-Related Dementia and Drug Abuse

艾滋病毒相关痴呆和药物滥用蛋白质组学试点中心

• 批准号: 7786174
• 负责人: ROBERT James COTTER
• 金额: $ 24.38万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7786174
• 关键词: Pilot; Proteomics; Center; HIV; Related

DESCRIPTION (provided by applicant): During the era of antiretroviral (ARV) therapy, the clinical syndrome of HIV associated dementia has evolved to a slower progression whereby clinical and radiological parameters lack the sensitivity for monitoring disease progression. This has posed unique challenges for conducing clinical trials with neuroprotective agents and for managing this patient population. The development of proteomics based biomarkers and surrogate markers are critical since they hold the promise of being sensitive to minor changes in brain function at a cellular level. Preliminary data from our group suggest that post translational modifications in proteins as a result of oxidative stress correlate with cognitive dysfunction. Recent advances in mass spectrometry (MS) have made it feasible to study large numbers of proteins simultaneously in biological fluids and to identify the proteins with relative ease. Taking advantage of these unique opportunities, the overarching theme of the proposed Pilot Proteomics Center for HIV-related Dementia and Drug Abuse is the discovery, identification and development of novel biomarkers for HIV-associated cognitive disorders and dementia in drug abusing patients. We have identified this as a high priority on the basis of our institutional strengths and continuing importance in clinical care. There is already a wealth of investigator-initiated HIV neuroscience research at Johns Hopkins University (JHU), especially focused on proteomics, pathogenesis, as well as significant expertise in clinical trial design. Despite this rich environment, currently there are no universally accepted, clinically accepted biomarkers available for HIV-associated cognitive disorders. Within the JHU Proteomics and HIV Neuroscience community, potential collaborations for biomarker development are currently limited by the lack of a strong central organizing structure, and specifically a facility to link different types of research, and to facilitate cross-disciplinary research. This Center will address these deficiencies. We propose three interactive projects, 1) Cerebrospinal Fluid (CSF) proteomic analysis will be performed on a well defined cohort of HIV infected drug abusers. A pilot study on the genetic markers that contribute to oxidative stress pathways will also be examined. 2) Similar proteomics analysis in CSF from SIV encephalitis model and 3) An in vitro human brain model of HIV infection and drug abuse.

描述（由申请人提供）：在抗逆转录病毒（ARV）治疗时代，HIV相关痴呆的临床综合征已发展为进展缓慢，临床和放射学参数缺乏监测疾病进展的敏感性。这给神经保护剂临床试验和管理该患者群体带来了独特的挑战。基于蛋白质组学的生物标志物和替代标志物的开发至关重要，因为它们有望在细胞水平上对大脑功能的微小变化敏感。我们小组的初步数据表明，氧化应激导致的蛋白质翻译后修饰与认知功能障碍相关。质谱 (MS) 的最新进展使得同时研究生物体液中的大量蛋白质并相对容易地识别蛋白质成为可能。利用这些独特的机会，拟议的艾滋病毒相关痴呆和药物滥用蛋白质组学试点中心的首要主题是发现、鉴定和开发药物滥用患者中艾滋病毒相关认知障碍和痴呆的新型生物标志物。基于我们的机构优势和在临床护理方面的持续重要性，我们已将其确定为高度优先事项。约翰·霍普金斯大学 (JHU) 已经开展了大量由研究者发起的 HIV 神经科学研究，特别关注蛋白质组学、发病机制以及临床试验设计方面的重要专业知识。尽管有这样丰富的环境，但目前还没有普遍接受的、临床上接受的生物标志物可用于治疗艾滋病毒相关的认知障碍。在约翰霍普金斯大学蛋白质组学和艾滋病毒神经科学界，生物标志物开发的潜在合作目前由于缺乏强大的中央组织结构而受到限制，特别是缺乏连接不同类型研究和促进跨学科研究的设施。该中心将解决这些缺陷。我们提出了三个互动项目，1）将对一组明确的 HIV 感染吸毒者进行脑脊液 (CSF) 蛋白质组分析。还将对有助于氧化应激途径的遗传标记进行初步研究。 2) SIV 脑炎模型的脑脊液中类似的蛋白质组学分析，3) HIV 感染和药物滥用的体外人脑模型。