Muscular Dystrophy Specialized Research Center: Project 2

项目2摘要 项目2的长期目标是使用以下方法确定肌营养不良聚糖病的自然史： 建立和发展临床措施，以优化临床护理为总体目标， 并提供信息和加强临床试验设计。这将在三个目标中实现。在目标1中， 我们将扩展我们目前的工作，以确定FKRP相关的自然历史， 营养不良性聚糖病我们跟踪了一组独特的患者，年龄从儿童早期到晚期， 成年后出现一系列FKRP突变我们将扩大和扩展对这一队列的评价 使用标准的、经过验证的结果测量。我们将与那些不再能够 由于疾病进展而旅行，远程评估使我们能够将运动 结果与真实世界终点（Ambassador丧失，呼吸支持需求）。我们还将 为此患者队列添加额外的评估中心以扩大队列并确认 对于FKRP相关患者人群，各研究中心的结局指标均有效。在目标2中， 将扩大我们对基因突变的肌营养不良症患者队列的随访， 除了FKRP。这些基因型中的每一种都非常罕见。我们会找出那些 相似的运动进展率，可能在基因非特异性临床研究中一起研究。 审判我们将每年从目标1和2中评价的患者中采集血液和尿液样本 这些样本的一个子集将用于目标3中的蛋白质组生物标志物鉴定。 先前的工作为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 与疾病进展相关。发现新的低丰度蛋白质将产生 新的候选人进行验证。

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.