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，但尚未针对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，这个 K-23 应用程序将满足这一需求，同时为 Heatwole 博士提供理想的环境，让他完成培训，成为肌肉疾病新型评估技术和实验疗法的独立研究员。具体来说，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）制定能够衡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）利用项目反应理论和先进的统计方法，从该问题集中开发出反应灵敏且可重复的工具； 5) 将该仪器纳入目前一项和两项计划中的针对强直性肌营养不良患者的临床试验； 6) 开发针对面肩肱型肌营养不良症和最近描述的 2 型强直性肌营养不良症的其他疾病特异性仪器。我们假设该项目将使研究人员能够通过一组有效、高效的疾病特定问题来衡量强直性肌营养不良的治疗反应，从而对公共健康产生积极影响。此外，通过这些项目，我们计划奠定开发其他肌肉疾病特定疾病工具所需的方法和技术框架。肌肉疾病研究领域受指导的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员和生活质量工具方面的权威提供了理想的媒介。 Heatwole 博士的职业发展将受到以下因素的促进： 1) 多学科专家导师团队； 2) 获得临床研究理学硕士学位的科学教学讲座和研讨会； 3) 直接使用临床和转化科学研究所专为开展和促进临床研究而设计的设施。 Heatwole 博士明确计划在 K-23 资助期结束时建立一个国家认可的强直性肌营养不良实验治疗和肌肉疾病生活质量仪器实验室。

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.