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

描述(申请人提供)：强直性肌营养不良症是世界上最常见的成人肌营养不良症。尽管有紧急需求，但还没有为这一人群开发出针对疾病的生活质量测量工具。如果获得资金，这一K-23应用程序将满足这一需求，同时为Heatwole博士完成他的培训提供理想的环境，成为肌肉疾病新评估技术和实验疗法的独立研究员。具体地说，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)开发能够测量这些领域的问题集；3)在纵向研究中测试这个问题集的响应性；4)利用项目反应理论和先进的统计方法从这个问题集中开发一个响应性和可重复性的工具；5)将这个工具整合到一个当前和两个计划中的强直性肌营养不良患者的临床试验中；以及6)开发更多针对面肩-肩周肌营养不良和最近描述的强直性肌营养不良2型的疾病特异性工具。我们假设，该项目将通过一组有效、有效的针对疾病的问题，使研究人员能够测量强直性肌营养不良症的治疗反应，从而积极塑造公共卫生。此外，通过这些项目，我们计划为开发更多针对肌肉疾病的疾病专用工具奠定所需的方法和技术框架。肌肉疾病研究领域的指导临床研究员职业发展奖为Heatwole博士成为独立的神经肌肉研究人员和生活质量工具方面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得到促进：1)多学科专家指导团队；2)临床调查理学硕士的科学教学讲座和研讨会；3)直接访问临床和翻译科学研究所专门为进行和促进临床研究而设计的设施。到K-23资助期结束时，Heatwole博士明确的计划是在强直性肌营养不良实验疗法和肌肉疾病生活质量仪器方面建立一个国家认可的实验室。

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.