The Development and Use of a Disease-Specific Instrument for Myotonic Dystophy

描述（由申请人提供）：强直性肌营养不良是世界上最常见的成人肌营养不良。尽管有紧急需求，但尚未为该人群开发出针对特定疾病的生活质量工具。如果获得资助，这项K-23申请将满足这一需求，同时为Heatwole博士提供理想的环境，以完成他的培训，成为一名独立的研究人员，研究新的评估技术和肌肉疾病的实验疗法。具体而言，我们的目标是：1）确定与强直性肌营养不良1型患者最相关的症状和功能区域; 2）开发能够测量这些领域的问题集; 3）在纵向研究中测试该问题集的响应性; 4）利用项目响应理论和先进的统计方法，从该问题集开发响应性和可重复性的工具; 5）将该仪器纳入强直性肌营养不良患者的一个当前和两个计划的临床试验中;和6）开发用于面肩肱型肌营养不良和最近描述的强直性肌营养不良2型的额外疾病特异性仪器。我们假设，该项目将积极塑造公共卫生，使研究人员能够通过一套有效的，有效的疾病特异性问题来衡量强直性肌营养不良的治疗反应。此外，通过这些项目，我们计划为开发针对肌肉疾病的其他疾病工具奠定必要的方法和技术框架。肌肉疾病研究指导临床研究者职业发展奖为Heatwole博士成为独立的神经肌肉研究人员和生活质量工具的权威提供了理想的媒介。Heatwole博士的职业发展将通过以下方式促进：1）专家多学科导师团队; 2）科学教学讲座和研讨会，导致临床研究科学硕士学位;以及3）直接访问临床和转化科学研究所的设施，专门用于开展和促进临床研究。到K-23资助期结束时，Heatwole博士明确计划建立一个国家认可的实验室，用于强直性肌营养不良实验治疗和肌肉疾病生活质量仪器。

DESCRIPTION (provided by applicant): Myotonic dystrophy is the most common adult muscular dystrophy in the world. Despite an emergent need, no disease-specific, quality-of-life instrument has ever been developed for this population. If funded, this K-23 application will address this need while providing the ideal environment for Dr. Heatwole to complete his training enroute to becoming an independent researcher of novel evaluation techniques and experimental therapeutics for muscle diseases. Specifically, it is our goal to: 1) Identify the symptomatic and functional areas most relevant to myotonic dystrophy type-1 patients; 2) Develop a question set capable of measuring these domains; 3) Test the responsiveness of this question set in a longitudinal study; 4) Utilize item response theory and advanced statistical methods to develop a responsive and reproducible instrument from this question set; 5) Incorporate this instrument into one current and two planned clinical trials of myotonic dystrophy patients; and 6) Develop additional disease-specific instruments for facioscapulohumeral muscular dystrophy and the more recently described myotonic dystrophy type-2. We hypothesize that this project will positively shape public health by enabling researchers to measure treatment responses in myotonic dystrophy via a valid, efficient set of disease-specific questions. In addition, through these projects, we plan to lay the methodological and technical framework needed for the development of additional disease-specific instruments for muscular disorders. The mentored clinical investigator career development award in muscle disease research provides the ideal medium for Dr. Heatwole to become an independent neuromuscular researcher and authority on instruments of quality-of-life. Dr. Heatwole's career development will be facilitated by: 1) An expert multidisciplinary mentorship team; 2) Scientific didactic lectures and workshops leading to a Master of Science in Clinical Investigation; and 3) By direct access to the Clinical and Translational Science Institute's facilities designed specifically to conduct and promote clinical research. By the end of the K-23 funding period it is Dr. Heatwole's explicit plan to have a nationally recognized laboratory established in both myotonic dystrophy experimental therapeutics and muscle disease quality-of-life instrumentation.