Longitudinal Study of Bone and Endocrine Disease in Children with MPS I, II, and VI: A Multi-Center Study of the Lysosomal Disease Network

大约85%的粘多糖病(MPS)I、II或VI型患者报告每周疼痛和 由于MPS相关的肌肉骨骼，50%-60%的人在日常生活能力上有明显的限制 尽管接受了酶替代疗法(ERT)的治疗，但这种疾病仍然存在。因此，迫切需要确定 减轻肌肉骨骼疾病负担的额外疗法，以改善健康和 MPS患者的生活质量。然而，疾病的进展需要量化，才能 确定新疗法的疗效。拟议的研究是一项多机构、为期5年的纵向研究 MPS中的肌肉骨骼疾病。长期目标是识别和测试新的治疗方法 MPS中的肌肉骨骼疾病。这项拟议的研究的目标是定量地描述 骨骼疾病的进展，并确定可以预测疾病严重程度或可以使用的生物标志物 作为MPS I、II和VI患者的治疗靶点。我们的中心假设是骨骼疾病将 随着时间的推移，炎症的生物标志物以及骨和软骨的更新将预测 随着时间的推移，骨骼疾病的严重性。具体目标是1)描述骨骼的进化过程 从童年到成年的疾病和2)确定炎症、骨骼的预后生物标记物 重塑和软骨更新可以预测骨骼疾病和身体受损的进展 功能。为了实现这些目标，参与者将每年接受骨健康测量(双功能)评估 X射线吸收测量法、外周定量计算机体层摄影术、髋部和脊柱X光片)、物理 功能(Biodex和握力测力仪测定的肌肉力量，运动范围测试，以及 身体功能和疼痛的问卷调查)，以及骨转换生物标志物的实验室测量， 软骨破裂和发炎。肌肉骨骼标准化测量数据库 MPS中的疾病将使该领域有效地推进对患有MPS的患者的治疗临床试验 国会议员。

Approximately 85% of individuals with Mucopolysaccharidosis (MPS) type I, II, or VI report weekly pain and 50-60% have significant limitations in their activities of daily living due to MPS related musculoskeletal disease despite treatment with enzyme replacement therapy (ERT). Thus there is a critical need to identify additional therapies to alleviate the burden of musculoskeletal disease in order to improve the health and quality of life of individuals with MPS. However, disease progression needs to be quantified to be able to determine efficacy of new therpies. The proposed study is a multi-institutional, 5-year, longitudinal study of musculoskeletal disease in MPS. The long-term goal is to identify and test new therapies for musculoskeletal disease in MPS. The objective of this proposed study is to quantitatively describe the progression of skeletal disease and identify biomarkers that either predict disease severity or could be used as therapeutic targets in individuals with MPS I, II, and VI. Our central hypothesis is that skeletal disease will progress over time and that biomarkers of inflammation, and bone and cartilage turnover, will predict the severity of skeletal disease over time. Specific aims are 1) to characterize the progression of skeletal disease from childhood into young adulthood and 2) to identify prognostic biomarkers of inflammation, bone remodeling, and cartilage turnover that can predict the progression of skeletal disease and impaired physical function. To achieve these aims, participants will be evaluated annually with measures of bone health (dualenery x-ray absorptiometry, peripheral quantitative computer tomography, hip and spine x-rays), physical function (muscle strength by Biodex and hand grip dynamometer, range of motion testing, and questionnaires of physical function and pain), and laboratory measurements of biomarkers of bone turnover, cartilage breakdown, and inflammation. A database of standardized measurements of musculoskeletal disease in MPS will allow the field to efficiently move forward with therapeutic clinical trials in patients with MPS.