2014 Sheep Request - Acquisition of a GC/MS/MS Instrument for State-of-the-Art Neurosteroid Quantification

2014 年绵羊请求 - 购买用于最先进的神经类固醇定量的 GC/MS/MS 仪器

• 批准号: 8951663
• 负责人: Christine E. Marx
• 金额: --
• 依托单位: DURHAM VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2015-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8951663
• 关键词: Acceleration; Autopsy; Basic Science; Biological Markers; Biological Psychiatry; Brain; Central Nervous System Diseases; Clinical Trials; Collaborations; Communication; Contract Services; Country; Development; Disease; Early Intervention; Funding; Future; Gold; Grant Review; Human; Immunoassay; Industry; Intervention; Investigation; Investigational Drugs; Journals; K-Series Research Career Programs; Laboratories; Lead; Legal patent; Manuscripts; Mass Fragmentography; Mass Spectrum Analysis; Medical center; Methodology; Neurologic; Pain; Peer Review; Post-Traumatic Stress Disorders; Preparation; Prevention strategy; Publications; Publishing; Research Personnel; Risk; Rodent Model; Role; Sampling; Schizophrenia; Secondary to; Services; Sheep; Techniques; Technology; Testing; Translating; Translations; Traumatic Brain Injury; Veterans; base; brain tissue; clinical investigation; cohort; improved; instrument; instrumentation; meetings; neurosteroids; novel therapeutic intervention; novel therapeutics; public health relevance; repaired; waiver

 DESCRIPTION (provided by applicant): Our Durham VA laboratory is fortunate to be one of few laboratories internationally with the capacity to quantify neurosteroids (endogenous molecules enriched in brain) using highly sensitive and specific `gold standard' mass spectrometry-based technologies. This state-of-the-art methodology was optimized and validated in our lab at the Durham VA Medical Center in 2004-2005, and the first peer-reviewed manuscripts utilizing this technology were published in 2006 (please see Appendix for listing, which includes 2 "Priority Communications" in Biological Psychiatry [impact factor 10.3] and 4 manuscripts in Neuropsychopharmacology [impact factor 7.8]). These publications involved collaborations with multiple VA investigators, both locally and across the country. Early neurosteroid biomarker investigations in rodent models and human postmortem brain tissue have been rapidly translated to proof-of-concept clinical trials testing neurosteroids as pharmacological interventions in Veteran cohorts with schizophrenia, traumatic brain injury, post-traumatic stress disorder, pain conditions, and other CNS disorders. We currently hold 4 FDA Investigational New Drug numbers for these studies, resulting from rapid translation of basic science `bench' efforts to clinical investigations. Also, pending patents related to these technologies focusing on use of neurosteroids and derivatives for the treatment of CNS conditions are co-owned by VA and Duke (208 waiver in place, see Appendix). Our first mass spectrometry instrumentation was purchased in 2001 - an Agilent 5973 gas chromatography/mass spectrometry (GC/MS) instrument that we are currently utilizing for our neurosteroid analytic projects (and with which we have achieved femtomolar sensitivity for neurosteroid quantification). Unfortunately, as of September 2014, Agilent will no longer support this GC/MS instrument with a service contract - because the GC/MS instrument was purchased over 12 years ago, it is considered "obsolete" from an industry support perspective, and thus Agilent will no longer guarantee repairs, service, or replacement of parts. As a result, current and future VA neurosteroid projects are at risk. Specifically, multiple VA studies and multiple VA investigators depend on this neurosteroid quantification capacity in order to complete the aims of funded VA Merit Review grants and Career Development Awards. Further, continued availability of this valuable technology to VA investigators will be pivotal to leveraging new scientific leads for development of novel therapeutics to treat conditions impacting large numbers of Veterans. It is also essential to have continued mass spectrometry capacity at VA because some high-impact journals are now requiring mass spectrometry approaches - and will no longer publish immunoassay methodologies (as of January 1, 2015 for J Clin Endocrinol Metab; see Appendix). The replacement of the GC/MS instrumentation is thus an urgent and critical scientific need for VA. We therefore request acquisition of a GC/MS/MS instrument in order to: 1.) Replace the current GC/MS instrument, for which we can no longer obtain a service contract and which will soon be rendered unusable secondary to absence of repair support and replacement parts 2.) Improve upon the current GC/MS methodology via acquisition of a GC/MS/MS instrument in order to: a. Further increase methodological sensitivity, as the GC/MS/MS instrument is even more sensitive than our current GC/MS instrument, thus likely requiring less labor-intensive sample preparation; thereby it would b. Increase our overall sample throughput and capacity, making it possible to collaborate with more VA investigators and to meet the ever-increasing demand for this technology (which certain high-impact journals are now also requiring for publication)

 描述（由申请人提供）： 我们位于弗吉尼亚州达勒姆的实验室很幸运，是国际上少数几个有能力使用高灵敏度和特异性的“金标准”质谱技术定量神经类固醇（大脑中富集的内源性分子）的实验室之一。2004-2005年，我们在达勒姆退伍军人医疗中心的实验室对这种最先进的方法进行了优化和验证，并于2006年发表了第一篇利用这种技术的同行评审论文（列表请参见附录，其中包括生物精神病学的2篇“优先通信”[影响因子10.3]和神经精神药理学的4篇手稿[影响因子7.8]）。这些出版物涉及与当地和全国各地的多个VA研究者的合作。啮齿动物模型和人类死后脑组织中的早期神经类固醇生物标志物研究已迅速转化为概念验证临床试验，该试验在患有精神分裂症、创伤性脑损伤、创伤后应激障碍、疼痛状况和其他CNS疾病的退伍军人队列中测试神经类固醇作为药理学干预。我们目前拥有4个FDA研究新药编号，这些研究是基础科学“实验室”工作快速转化为临床研究的结果。此外，VA和杜克共同拥有与这些技术相关的未决专利，这些技术侧重于使用神经类固醇和衍生物治疗CNS疾病（208项豁免，见附录）。我们的第一台质谱仪器是在2001年购买的-Agilent 5973气相色谱/质谱（GC/MS）仪器，我们目前正在使用我们的神经类固醇分析项目（我们已经实现了神经类固醇定量的飞摩尔灵敏度）。不幸的是，截至2014年9月，安捷伦将不再通过服务合同支持此GC/MS仪器-因为GC/MS仪器是在12年前购买的，从行业支持的角度来看，它被认为是“过时的”，因此安捷伦将不再保证维修、服务或更换部件。因此，目前和未来的VA神经类固醇项目处于危险之中。具体而言，多个VA研究和多个VA调查人员依赖于这种神经类固醇定量能力，以完成资助VA优异评审赠款和职业发展奖的目标。此外，这种有价值的技术对VA研究人员的持续可用性将是利用新的科学线索开发新疗法以治疗影响大量退伍军人的疾病的关键。VA继续拥有质谱分析能力也是至关重要的，因为一些高影响力的期刊现在需要质谱分析方法-并且将不再发表免疫分析方法（自2015年1月1日起，J Clin Endocrinol Metab;见附录）。因此，更换GC/MS仪器是VA的迫切和关键的科学需求。因此，我们请求采购GC/MS/MS仪器，以便：1.更换现有的GC/MS仪器，我们无法再获得服务合同，并且由于缺乏维修支持和更换部件，该仪器很快将无法使用2）。通过购买GC/MS/MS仪器来改进当前的GC/MS方法，以便：进一步提高方法灵敏度，因为GC/MS/MS仪器比我们目前的GC/MS仪器更灵敏，因此可能需要更少的劳动密集型样品制备;因此，它将B。提高我们的整体样本吞吐量和容量，使我们能够与更多的VA研究人员合作，并满足对该技术不断增长的需求（某些高影响力期刊现在也要求出版）