Research in Congenital Muscle Disease

先天性肌肉疾病的研究

• 批准号: 8940026
• 负责人: Katherine Meilleur
• 金额: $ 43.68万
• 依托单位: NATIONAL INSTITUTE OF NURSING RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8940026
• 关键词: Activities of Daily Living; Adverse effects; Affect; Africa South of the Sahara; Age; Articular Range of Motion; Award; Biological; Birth; Brain; Calibration; Caregivers; Cerebral Palsy; Cessation of life; Charge; Child; Childhood; Classification; Clinic; Clinical; Clinical Investigator; Clinical Trials; Clinical Trials Design; Collagen Type VI; Contracture; Country; Data; Data Analyses; Data Storage and Retrieval; Development; Disease; Disease Progression; Doctor of Pharmacy; Enrollment; Fatigue; Floor; Focus Groups; Frequencies; Future; Generic Drugs; Genetic; Goals; Home environment; Impairment; Injury; Institution; Institutional Review Boards; Interview; Joints; Laminin; Left; Legal Guardians; Logistics; Magnetic Resonance Imaging; Manuscripts; Measurement; Measures; Medical Research; Merosin; Molecular; Mosaicism; Motor; Movement; Muscle; Muscle Weakness; Muscular Dystrophies; Mutation; Myopathy; National Institute of Neurological Disorders and Stroke; Neuromuscular Diseases; Neuromuscular Manifestations; Nursing Research; Nursing Students; Outcome; Outcome Assessment; Outcome Measure; Paralysed; Parents; Participant; Passive Range of Motion function; Pathologic; Patient Recruitments; Patients; Performance; Peripheral Nervous System; Pharmacy Students; Physical Medicine; Physical therapy; Pilot Projects; Positioning Attribute; Postdoctoral Fellow; Protocols documentation; Proxy; Published Comment; Publishing; Qualitative Methods; Quality of life; Questionnaires; Rare Diseases; Reporting; Research; Research Personnel; Respiratory Insufficiency; Severities; Spinal Muscular Atrophy; Steroids; Stress; Students; Symptoms; System; Telephone; Testing; Time; Tissues; Translating; Translations; Travel; Ultrasonography; Universities; Validation; Walking; Work; antioxidant therapy; base; bench to bedside; burden of illness; cohort; congenital muscular dystrophy; congenital myopathy; disorder subtype; drug efficacy; dystroglycanopathy; functional disability; health related quality of life; improved; insight; interest; motor impairment; neurogenetics; neuromuscular; novel; programs; receptor; research clinical testing; respiratory; response; scoliosis; success; theories; tool

Over the past year, I continued as an Assistant Clinical Investigator in the Tissue Injury Branch of the NINR, a position I started in September of 2012. Over the past year, I have enrolled participants in two active protocols. The first one is a study to develop the first proxy motor outcome assessment in young children with neuromuscular disease, entitled Development of a Proxy Motor Outcome Measure in Young Children with Neuromuscular Disease. Eighteen parents (or legal guardians) were enrolled and were interviewed by phone using qualitative methods. These results were then analyzed and the major themes were presented to a focus group of 10 experts in pediatric neuromuscular disease. The next step is for the focus group comments to be incorporated into the development of specific items for this novel scale of proxy reported motor function in young children age birth through 5 years. The goal is to use the new scale in future clinical trials to decrease parent stress related to travel to research centers for clinical trials and to improve ecological validity of motor function by utilizing parent insight in the home setting. My team also enrolled 32 pediatric participants and 29 parents in the active second protocol, The Calibration and Validation of the PROMIS and Neuro-QOL Questionnaires in Cerebral Palsy and Congenital Muscular Dystrophy. Preliminary item response theory analyses are underway with Columbia University, the collaborating institution, to validate these two questionnaires for use in neuromuscular disease patients. A third study received the Bench to Bedside Award this past year and is currently under IRB review. This is a clinical trial of antioxidant therapy in patients with RYR1 congenital myopathy and will take place over the next two years. This summer, I hired a postdoc who also has a doctorate in physical therapy for this trial as we work closely with the Department of Rehabilitation Medicine in the Clinical Center for this trial. I am also an Associate Investigator on an NINDS protocol entitled Clinical and Molecular Manifestations of Neuromuscular and Neurogenetic Disorders of Childhood. As part of this protocol, I took a 5-year project with me from NINDS when left NINDS and started with NINR. The project is a 5-year study of clinical outcome measures in two subtypes of congenital muscular dystrophy, Collagen VI-Related Myopathy and Laminin 2 Related Muscular Dystrophy. This past June 2014, I organized the 5th and final year of the study with my research team, a postbac fellow, a research nurse, and two summer students, including a nursing student and a doctor of pharmacy student. The study brought 35 patients to the Clinical Center over a week mid June in which the patients under went testing including motor function scales and timed tests, muscle and brain MRI, muscle ultrasound, and quality of life questionnaires. I was in charge of the logistics, patient recruitment, and data storage and analysis of this large project involving approximately 30 clinicians and researchers from across the country. A first author manuscript summarizing the first two-year pilot study of this 5-year longitudinal was accepted last month in Neuromuscular Disorders. Other manuscripts published this past year include: Clinical, pathologic, and mutational spectrum of dystroglycanopathy caused by LARGE mutations (Meilleur et al., J Neuropath & Experim Neurol, 2014); Genetics of low spinal muscular atrophy carrier frequency in sub-Saharan Africa (Sangare et al., Ann of Neurol, 2014); English cross-cultural translation and validation of the NM-Score; a system for motor function classification in patients with neuromuscular diseases (Vuillerot, C., Meilleur, K. et al., Arch of Phys Med & Rehab, 2014); Mosaicism for dominant collagen VI mutations as a cause for intra-familial phenotypic variability Donkervoort et al., Hum Mut, 2014).

在过去的一年里，我继续担任NINR组织损伤分支的助理临床研究员，我于2012年9月开始担任该职位。 在过去的一年里，我招募了两个活跃协议的参与者。第一项研究是在患有神经肌肉疾病的幼儿中开发第一个代理运动结果评估，题为神经肌肉疾病幼儿代理运动结果测量的开发。 18名家长（或法律的监护人）被招募，并通过电话采访使用定性方法。 然后对这些结果进行分析，并将主要主题提交给由10名儿科神经肌肉疾病专家组成的焦点小组。下一步是将焦点小组的意见纳入到这一新的代理报告的运动功能量表的具体项目的开发中，该量表适用于出生至5岁的幼儿。 我们的目标是在未来的临床试验中使用新的量表，以减少与前往研究中心进行临床试验相关的父母压力，并通过在家庭环境中利用父母的洞察力来提高运动功能的生态有效性。 我的团队还招募了32名儿科参与者和29名家长参加第二个方案，即脑瘫和先天性肌营养不良症的PROMIS和神经QOL量表的校准和验证。 初步的项目反应理论分析正在进行与哥伦比亚大学，合作机构，以验证这两个问卷用于神经肌肉疾病患者。 第三项研究在过去的一年中获得了“从实验室到床边”奖，目前正在接受IRB审查。 这是一项抗氧化治疗RYR 1先天性肌病患者的临床试验，将在未来两年进行。 今年夏天，我聘请了一位博士后，他也拥有物理治疗博士学位，因为我们与临床中心的康复医学系密切合作。 我也是NINDS方案的副研究员，该方案题为儿童神经肌肉和神经遗传性疾病的临床和分子表现。 作为该协议的一部分，我在离开NINDS并开始NINR时从NINDS开始了一个为期5年的项目。该项目是一项为期5年的研究，对先天性肌营养不良症的两种亚型（胶原VI相关性肌病和层粘连蛋白2相关性肌营养不良症）的临床结果进行测量。 过去的2014年6月，我与我的研究团队组织了第五年也是最后一年的研究，一名postbac研究员，一名研究护士，和两名暑期学生，包括一名护理学生和一名药学博士。该研究在6月中旬的一周内将35名患者带到临床中心，患者接受了包括运动功能量表和定时测试，肌肉和大脑MRI，肌肉超声和生活质量问卷在内的测试。 我负责这个大型项目的后勤、患者招募、数据存储和分析，该项目涉及来自全国各地的大约30名临床医生和研究人员。 第一作者手稿总结了这项为期5年的纵向研究的第一个为期两年的试点研究，上个月在神经肌肉疾病中被接受。 过去一年发表的其他手稿包括：由LARGE突变引起的肌营养不良聚糖病的临床、病理和突变谱（Meilovich等人，J Neuropath & Experim Neurol，2014）; Genetics of low spinal muscular atrophy carrier frequency in sub-Saharan Africa（Sangare et al. Ann of Neurol，2014）; NM评分的英语跨文化翻译和验证;神经肌肉疾病患者的运动功能分类系统（Vuillerot，C.，Meillem，K.例如，Arch of Phys Med & Rehab，2014）;作为家族内表型变异性的原因的显性胶原VI突变的嵌合体Donkervoort等人，Mut，2014）。