Innovative Statistical Models for Development of First Huntington's Disease Progression Risk Assessment Tool

用于开发第一个亨廷顿病进展风险评估工具的创新统计模型

• 批准号: 9224488
• 负责人: Tanya Pamela Garcia
• 金额: $ 19.08万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2019-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9224488
• 关键词: AIDS Dementia Complex; Alzheimer' s Disease; Americas; Area; Assessment tool; Attenuated; Big Data; Biological Markers; Biometry; Books; Brain; Brain region; Clinical; Clinical Trials; Clinical Trials Design; Complex; Data; Data Set; Deterioration; Development; Diagnosis; Dimensions; Disease; Disease Progression; Early Intervention; Future; Generations; Goals; Human Biology; Huntington Disease; Impaired cognition; Impairment; Individual; Knowledge; Lead; Learning; Magnetic Resonance Imaging; Masks; Measurement; Measures; Medicine; Mendelian disorder; Mentors; Methodology; Methods; Modeling; Motor; Nerve Degeneration; Neurodegenerative Disorders; Neuroepidemiology; Neurologic; Neurology; Neurosciences; Outcomes Research; Parkinson Disease; Pattern; Penetrance; Performance; Precision Medicine Initiative; Publications; Research; Research Personnel; Risk; Risk Assessment; Sample Size; Societies; Statistical Data Interpretation; Statistical Methods; Statistical Models; Structure; Symptoms; System; Texas; Therapeutic Intervention; Time; Training; United States National Institutes of Health; Universities; Vision; base; behavioral neurology; career; disease diagnosis; distinguished professor; improved; individual patient; innovation; model development; motor disorder; neuroimaging; professor; protein misfolding; prototype; skills; statistics; technology training; therapy design; tool; treatment strategy; user friendly software; user-friendly

Huntington's disease (HD) is a progressive, neurodegenerative disorder that can be genetically diagnosed years before clinical symptoms onset. This presents groundbreaking opportunities to learn the overall, dynamic progression of HD which is critical to the timing of therapeutic interventions and design of effective clinical trials. Despite advancements in this area, significant gaps exist about the transitional period from premanifest to mani- 7. Project Summary/Abstract fest HD, particularly how and when overt clinical symptoms and neurological deterioration develop. As part of the candidate's long-term goal to become an independent, lead expert biostatistician for neurodegenerative diseases, the overarching goal of this K01 is to acquire training in the disease-related background and quantitative analyti- cal skills to develop innovative methods that target new discoveries of HD progression. The candidate, Dr. Tanya P. Garcia, is a Huntington's Disease Society of America (HDSA) Human Biology Project Fellow (2013-2015) and has assembled a team of outstanding mentors and collaborators who will provide training to acquire the skills she lacks for an independent, biostatistically-focused, neuroscience career. Her two primary mentors are Dr. Karen Marder and Dr. Raymond J. Carroll. Dr. Marder is the Sally Kerlin Professor of Neurology at Columbia University with over 300 publications in behavioral neurology, neuroepidemiology and neurodegenerative diseases including Huntington's, Alzheimer's, Parkinson's and HIV dementia. Dr. Carroll is Distinguished Professor of Statistics at Texas A&M University with over 400 publications and 5 books in multiple statistics areas, particularly in those needed for this proposal. To conduct high-level research that fills significant gaps about HD progression knowl- edge, Dr. Garcia proposes in-depth training (i) To learn the latest developments and challenges in clinical and neurological understanding of HD to fine-tune statistical methodology; (ii) To obtain proficiency in analysis of cor- related, longitudinal, big data; and (iii) To develop programming expertise to make the proposed methods acces- sible to neuroscience investigators in user-friendly software. Training in these areas directly support Dr. Garcia's research aims which are (i) To improve prediction of HD motor-diagnosis by modeling the time-varying effects of multiple clinical performance measures; (ii) To improve identification of disease-relevant brain regions in relation to HD motor-diagnosis by modeling the spatial-temporal brain structure; and (iii) To develop the first generation of a HD Progression Risk Assessment Tool (HD-PRAT). Expected research outcomes include models that support President Obama's Precision Medicine Initiative in that they adhere to “2P's” of the NIH New Strategic Vision of the “4P's” of Medicine: they will offer promising ways to Predict the pattern and intensity of an individual's clinical and neurological changes over time; and increase the capacity to Personalize early intervention based on these learned predictions. Having the models available in user-friendly HD-PRAT is of high

亨廷顿氏病（HD）是一种进行性神经退行性疾病，可以通过基因诊断 在临床症状出现前10年。这提供了开创性的机会，学习整体，动态 HD的进展，这对治疗干预的时机和有效临床试验的设计至关重要。 尽管在这一领域取得了进展，但从预显到mani的过渡期存在重大差距。 7.项目总结/摘要 Fest HD，特别是如何以及何时出现明显的临床症状和神经系统恶化。的一部分 候选人的长期目标是成为神经退行性疾病的独立，领先的专家生物统计学家， 该K 01的总体目标是获得疾病相关背景和定量分析方面的培训， 开发针对HD进展新发现的创新方法的技能。候选人谭雅医生 P.加西亚是美国亨廷顿病协会（HDSA）人类生物学项目研究员（2013-2015）， 已经组建了一个由优秀的导师和合作者组成的团队，他们将提供培训，以获得她所需要的技能。 缺乏一个独立的，以生物医学为中心的神经科学事业。她的两个主要导师是凯伦博士 Marder和Raymond J.卡罗尔博士。Marder博士是哥伦比亚大学神经病学的Sally Kerlin教授 在行为神经学、神经流行病学和神经退行性疾病方面发表了300多篇论文， 亨廷顿氏症，老年痴呆症，帕金森氏症和艾滋病痴呆症。卡罗尔博士是统计学的杰出教授， 德克萨斯A&M大学拥有超过400种出版物和5本多个统计领域的书籍，特别是在那些 这一提议所需的。进行高水平的研究，填补有关HD进展知识的重大空白- Garcia博士建议进行深入培训（i）了解临床和医学领域的最新发展和挑战， 神经系统对HD的理解，以微调统计方法;（ii）在分析心脏病方面获得优势， 相关的，纵向的，大数据;和（iii）发展编程专业知识，使拟议的方法获得- 神经科学研究人员可以使用用户友好的软件。在这些领域的培训直接支持加西亚博士的 研究目的是：（i）通过对以下因素的时变影响进行建模， 多个临床性能指标;（ii）改善与疾病相关的大脑区域的识别 通过对时空大脑结构建模来进行高清运动诊断;以及（iii）开发第一代 HD进展风险评估工具（HD-PRAT）。预期的研究成果包括支持 奥巴马总统的精准医学倡议，因为他们坚持“2 P的”国家卫生研究院的新战略愿景， 医学的“4P”：它们将提供有希望的方法来预测个人临床症状的模式和强度。 随着时间的推移，神经系统的变化;并根据这些变化增加个性化早期干预的能力 学习预测拥有用户友好的HD-PRAT模型，