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: 10442637
• 负责人: Katherine Dianne Mathews
• 金额: $ 41.8万
• 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/10442637
• 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; remote assessment; 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总结 项目 2 的长期目标是使用以下方法定义肌营养不良症的自然史： 已建立和不断发展的临床措施，总体目标是优化临床护理， 并告知和加强临床试验设计。这将通过 3 个目标来实现。在目标 1 中， 我们将扩展当前的工作来定义 FKRP 相关的自然历史 肌聚糖病。我们跟踪一组独特的从幼儿期到晚期的患者 成年后出现一系列 FKRP 突变。我们将扩大和扩展对该群体的评估 使用标准的、经过验证的结果测量。我们将让那些无法再参与的人参与进来 通过远程评估因疾病进展而旅行，使我们能够将运动联系起来 现实世界终点的结果（失去行走能力、需要呼吸支持）。我们还将 为该患者队列添加额外的评估站点以扩大队列并确认 结果测量对于 FKRP 相关患者群体在各个地点均有效。在目标 2 中，我们 将延长我们对一组基因突变的肌营养不良患者的随访 除了 FKRP 之外。这些基因型中的每一种都非常罕见。我们将确定具有共同特征的群体 相似的运动进展率可以在基因非特异性临床中一起研究 试验。我们将从目标 1 和 2 中评估的患者中收集年度血液和尿液样本 这些样本的一部分将用于目标 3 中的蛋白质组生物标志物鉴定。 之前的工作为 FKRP 突变患者确定了一组候选蛋白质生物标志物。 我们将在一组单独的患者样本中验证这些，并确定是否有任何变化 与疾病进展相一致。新的极低丰度蛋白质的发现将产生 用于验证的新候选者。