A New Approach to ALS

治疗 ALS 的新方法

• 批准号: 8259404
• 负责人: Cassie S Mitchell
• 金额: $ 12.83万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8259404
• 关键词: Acute; Address; Adult; Affect; Amyotrophic Lateral Sclerosis; Cessation of life; Chronic; Clinical; Clinical Data; Clinical Treatment; Clinical assessments; Combined Modality Therapy; Complex; Data Analyses; Databases; Disease; Disease Progression; Electrophysiology (science); Felis catus; Foundations; Functional disorder; Future; Individual; Lead; Literature; Mentors; Meta-Analysis; Methodology; Methods; Modeling; Motor Neurons; Nerve Degeneration; Neurodegenerative Disorders; Outcome; Pathology; Patients; Pharmaceutical Preparations; Physiological; Physiology; Positioning Attribute; Process; Property; Publishing; Research; Resolution; Riluzole; Techniques; Therapeutic; Training; Work; career; career development; clinically relevant; expectation; experience; in vivo; innovation; insight; neuropathology; novel; novel strategies; predictive modeling; public health relevance; research study; response; theories; treatment strategy

DESCRIPTION (provided by applicant): The scientific objective of this project is to develop a comprehensive quantitative framework of ALS from which initiation/progression can be examined and combination treatments be quantitatively generated, predicted, and prioritized. We hypothesize that there exists a pathophysiological spectrum of interactions that can only be viewed when physiology and pathology are examined together, and it is this set of interactions that holds the key to unlocking both our understanding of ALS and especially its treatment with synergistic, interaction-exploiting combination treatments. Our approach is to integrate the wealth of information derived from the ALS and related physiological literature, in conjunction with traditional experimental and clinical observations, to develop a comprehensive framework of ALS-relevant motoneuron pathophysiology using our innovative "dynamic meta-analysis" technique, referred to as relational modeling. The significance of this proposal is that it will generate new and exciting ALS insight and treatment strategies in a high-throughput manner not possible with traditional experimentation alone. The research aims consist of developing a quantitative framework of ALS using both the literature and clinical data analysis (aim 1); assess the effects of riluzole on in vivo electrophysiology (aim 2); and generating and quantitatively assessing combination treatment strategies within the developed framework (aim 3). The primary scientific outcomes of this proposal include a comprehensive model of ALS motoneuron pathophysiology, mechanistic insight into the actions of riluzole and a prioritized list of potential therapeutic strategies. The career development outcomes of this proposal include hands-on training in in vivo neuroelectrophysiology, clinical data analysis, and their integration with theory to make clinically relevant predictions. PUBLIC HEALTH RELEVANCE: In this project, we use an innovative method, our form of "dynamic meta-analysis" referred to as relational modeling that integrates theory, experimental, and clinical data analysis to create a quantitative framework of ALS from which clinically relevant predictions can be made regarding pathology progression. Using this developed framework, we will generate and quantitatively assess novel ALS treatments, both singly and in combination. The scientific outcome of this proposal is a prioritized list of ALS therapeutic strategies, with the career development outcomes being hands-on training in traditional neuroelectrophysiology and clinical neurodegenerative assessment.

描述（由申请人提供）：该项目的科学目标是开发一个ALS的综合定量框架，可以从中检查启动/进步，并在定量生成，预测和优先级。我们假设存在一种相互作用的病理生理谱，只有在一起检查生理学和病理学时才能查看，而正是这组相互作用始终是释放我们对ALS的理解，尤其是与协同相互作用的治疗的关键。利用组合治疗。我们的方法是将来自ALS和相关生理文献获得的大量信息与传统的实验和临床观察结合在一起，以使用我们的创新性“动态荟萃分析”技术来开发与ALS相关的Motoneuron Pathyophyology的综合框架，并将其引用。作为关系建模。该提案的意义在于，仅通过传统的实验，它将以高通量的方式产生新的和令人兴奋的ALS洞察力和治疗策略。该研究的目的包括使用文献和临床数据分析开发ALS的定量框架（AIM 1）；评估Riluzole对体内电生理学的影响（AIM 2）；并在开发框架内生成和定量评估组合处理策略（AIM 3）。该建议的主要科学结果包括ALS运动神经元病理生理学的综合模型，对Riluzole行为的机理见解以及优先的潜在治疗策略清单。该提案的职业发展成果包括体内神经电机生理学，临床数据分析以及与理论的整合以做出临床相关预测的动手培训。 公共卫生相关性：在这个项目中，我们使用一种创新方法，即我们的“动态荟萃分析”形式，称为关系建模，将理论，实验性和临床数据分析整合在一起，以创建ALS的定量框架，从而从中进行临床相关的预测可以就病理进展而制作。使用此开发的框架，我们将单独和合并生成和定量评估新颖的ALS处理。该提案的科学结果是ALS治疗策略的优先级清单，其职业发展成果是传统神经电机生理学和临床神经退行性评估方面的动手培训。