Treatment of Multiple Sclerosis

多发性硬化症的治疗

• 批准号: 6963466
• 负责人: ANTHONY T REDER
• 金额: $ 13.77万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6963466
• 关键词: T cell receptor; antiantibody; biological signal transduction; clinical research; evoked potentials; human subject; human therapy evaluation; immunotherapy; interferon beta; longitudinal human study; lymphocyte; magnetic resonance imaging; multiple sclerosis; nervous system disorder therapy; neurophysiology; patient oriented research; statistics /biometry; transcription factor

DESCRIPTION (provided by applicant): This proposal will enhance the PI's background in trial design and statistics and improve his mentoring skills. It allows time for mentoring fellows who will receive extensive training in statistics and trial design, in the clinical presentation MS, and in essential lab techniques to aid in investigation of immunological mechanisms in MS. Fellows are an integral part of all aspects of trial design, execution, and analysis of two investigator-initiated trials. The first trial determines if anti-VLA-4 antibodies will slow primary progressive MS-a form of MS refractory to all current therapy. Drug infusion, monitoring, and processing of blood for gene profiling will take place in the CRC. Therapeutic effects will be measured with a novel combination of measures including our MS-specific quality of life scale, cervical spinal cord MRI volume and magnetization transfer ratio, and neurophysiological function (motor evoked potentials and autonomic testing), plus neurological exams. A second, longitudinal trial extends our recent finding of defective interferon-beta signaling in lymphocytes of clinically active MS patients. We will determine if subnormal levels of an activated transcription factor in lymphocytes reflects disease state, predicts transition to progression, and marks responses to therapy. In parallel, we will determine the molecular basis of the IFN-beta signaling defect, whether it reflects a fundamental biological abnormality affecting clinical manifestations, and whether it can be reversed by drug therapy. Long-term goals for the PI are to develop and mentor skills in trial design and statistical analysis in order to craft investigator-initiated trials that examine basic mechanisms of disease and novel therapies. The PI will receive pharmacogenomics and proteomics training, an important part of future investigator-initiated trials of this complex disease. He will also expand and improve clinical fellowship training in MS in conjunction with the CRC, Dept. of Health Studies and its K30 program, and educate fellows in trial design, statistics, and all neurologic aspects of MS.

描述（由申请人提供）：该提案将增强 PI 在试验设计和统计方面的背景，并提高他的指导技能。它为指导研究员提供了时间，他们将接受统计和试验设计、多发性硬化症临床表现和基本实验室技术方面的广泛培训，以帮助研究多发性硬化症的免疫机制。研究员是两项研究者发起的试验的试验设计、执行和分析各个方面不可或缺的一部分。 第一项试验确定抗 VLA-4 抗体是否会减缓原发性进行性多发性硬化症（一种对所有现有疗法均无效的多发性硬化症）。药物输注、监测和血液处理以进行基因分析将在 CRC 内进行。治疗效果将通过新的测量组合来衡量，包括我们的多发性硬化症特定生活质量量表、颈脊髓 MRI 体积和磁化转移比、神经生理功能（运动诱发电位和自主神经测试）以及神经系统检查。 第二项纵向试验扩展了我们最近发现的临床活动性多发性硬化症患者淋巴细胞中存在缺陷的干扰素 β 信号传导的结果。我们将确定淋巴细胞中激活的转录因子的低于正常水平是否反映了疾病状态，预测了向进展的转变，并标记了对治疗的反应。与此同时，我们将确定 IFN-β 信号传导缺陷的分子基础，它是否反映了影响临床表现的基本生物学异常，以及是否可以通过药物治疗逆转。 PI 的长期目标是发展和指导试验设计和统计分析方面的技能，以便精心设计由研究者发起的试验，以检查疾病的基本机制和新疗法。 PI 将接受药物基因组学和蛋白质组学培训，这是未来研究者发起的这种复杂疾病试验的重要组成部分。他还将与 CRC、健康研究部及其 K30 项目合作，扩大和改进多发性硬化症临床研究员培训，并对研究员进行试验设计、统计和多发性硬化症所有神经学方面的教育。