Muscular Dystrophy Specialized Research Center: Project 2

肌营养不良症专业研究中心：项目2

• 批准号: 10238933
• 负责人: Katherine Dianne Mathews
• 金额: $ 30.17万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-08 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10238933
• 关键词: Address; Adult; Age; Agreement; Biological Markers; Blood; Clinical; Clinical Trials; Clinical Trials Design; Data Collection; Disease; Disease Progression; Evaluation; Functional disorder; Genes; Genotype; Goals; Grouping; Heterogeneity; Individual; Interview; Life; Limb structure; Longitudinal Studies; Measures; Medical; Motor; Muscular Dystrophies; Mutation; Natural History; Outcome; Outcome Measure; Participant; Patient Care; Patients; Peptides; Performance; Phenotype; Physical assessment; Plasma; Proteins; Proteomics; Protocols documentation; Rare Diseases; Research; Research Personnel; Sampling; Site; Standardization; Study Subject; Techniques; Telephone; Therapy Clinical Trials; Travel; Urine; Validation; Work; aged; base; biomarker identification; candidate marker; candidate validation; clinical care; clinical phenotype; cohort; congenital muscular dystrophy; disease phenotype; dystroglycanopathy; early childhood; follow-up; fukutin related protein; insight; meetings; minimally invasive; novel; patient biomarkers; patient population; patient stratification; protein biomarkers; respiratory; telehealth

Project 2 Summary The long-term goal of Project 2 is to define the natural history of the dystroglycanopathies using established and evolving clinical measures, with the overall objective of optimizing clinical care, and informing and enhancing clinical trial design. This will be accomplished in 3 Aims. In Aim 1, we will extend our current work to define the natural history of FKRP-related dystroglycanopathy. We follow a unique cohort of patients aged early childhood through late adulthood with a range of FKRP mutations. We will expand and extend evaluation of this cohort using standard, validated outcome measures. We will engage those who are no longer able to travel due to disease progression with remote assessments allowing us to relate motor outcomes to real-world endpoints (loss of ambulation, need for respiratory support). We will also add additional evaluation sites for this patient cohort to expand the cohort and confirm that the outcome measures are valid across sites for the FKRP-related patient population. In Aim 2, we will extend our follow up of a cohort of dystroglycanopathy patients with mutations in genes other than FKRP. Each of these genotypes is quite rare. We will identify cohorts that share similar rates of motor progression who might be studied together in gene non-specific clinical trials. We will collect annual blood and urine samples from patients evaluated in Aims 1 and 2 and a subset of these samples will be used in Aim 3 for proteomic biomarker identification. Previous work identified a set of candidate protein biomarkers for patients with FKRP mutations. We will validate these in a separate set of patient samples and determine if any change in concert with disease progression. Discovery of new very low abundance proteins will produce novel candidates for validation.

项目2摘要 项目2的长期目标是使用使用dystroglycanopathies的自然历史 建立和不断发展的临床指标，其总体目的是优化临床护理， 并告知和增强临床试验设计。这将在3个目标中实现。在AIM 1中， 我们将扩展当前的工作以定义与FKRP相关的自然历史 dystroglycanopathy。我们遵循独特的童年患者的独特群体，直到迟到 成年，具有一系列FKRP突变。我们将扩展和扩展该队列的评估 使用标准，经过验证的结果指标。我们将吸引那些不再能够 由于疾病的进展和远程评估而导致的旅行，使我们能够联系电动机 现实世界中终点的结果（失去行动，需要呼吸支持）。我们也会 为该患者队列添加其他评估站点，以扩大同类群体并确认 与FKRP相关的患者人群之间的结果措施在各个地点之间都是有效的。在AIM 2中，我们 将扩大我们对基因突变的多糖瘤病患者的随访 除了FKRP。这些基因型中的每一个都很少见。我们将确定共享的队列 可能在基因非特异性临床中一起研究的运动进展速率相似 试验。我们将从AIMS 1和2中评估的患者中收集每年的血液和尿液样本 这些样品的一个子集将用于AIM 3中，以用于蛋白质组学生物标志物鉴定。 先前的工作确定了一套针对FKRP突变患者的候选蛋白生物标志物。 我们将在一组单独的患者样本中验证它们，并确定是否有任何变化 与疾病进展的音乐会。发现新的非常低的丰度蛋白会产生 验证的新颖候选人。