Longitudinal Studies of Brain Structure and Function in MPS Disorder

粘多糖沉积症是一种溶酶体疾病，通常从儿童开始逐渐影响体内大多数器官系统。最近的治疗进展已经改善了这些功能障碍中的一些，但值得注意的是，脑和骨一直难以治疗。 脑异常的MPS疾病，其中知之甚少。 本研究的目标是： 1)确定中枢神经系统（CNS）结构和功能异常，并测量治疗和未治疗MPS疾病患者随时间推移的生活质量（QOL）。我们将通过对北美核心中心（构成溶酶体疾病网络（LDN））入组的患者进行纵向研究来实现这一目标。我们假设，具体的和本地化的神经影像学和神经心理学的结果和他们的关系将是不同的每一个MPS疾病。此外，如果不治疗，功能将下降，结构将以可预测的方式随时间改变，并且将与异常部位和疾病阶段相关 2)开发变化的定量测量;包括直接测量神经心理功能、替代MRI标记物和生物标记物，以测量疾病阶段和治疗结果。 3)检查独立变量（如首次治疗时的年龄、疾病严重程度、医学异常类型、突变、医学事件、感觉异常等）对功能和结构结果脑变量以及生活质量的影响程度。 4)研究ERT、HSCT、底物减少和其他姑息和康复疗法等治疗如何不同地影响CNS结构和功能以及生活质量（QOL）。 研究方法：在前两年，本研究将入组来自8家临床试验机构的70例儿童，并在5年内进行随访; 30例MPS I、20例MPS II和20例MPS VI。每名儿童将在五年内每年接受至少3次或可能4次随访。定量神经影像学和神经心理学 协议将用于收集数据以及可能影响这些措施的相关医疗和环境变量。还将收集可能对变化敏感的新生物标志物。将分析数据以确定中枢神经系统异常的部位、指标对变化和疾病进展的敏感性，并确定促成这些结局的变量。

The mucopolysaccharidoses are lysosomal disorders that progressively affect most organ systems in the body usually beginning in childhood. Recent treatment advances have produced amelioration of some of these malfunctions, but notably brain and bone have been difficult to treat. This research addresses the brain abnormalities in the MPS disorders about which little is known. The objectives of this research are: 1) to identify abnormalities of central nervous system (CNS) structure and function as well as to measure quality-of-life (QOL) in both treated and untreated patients with MPS disorders over time. We will accomplish this through longitudinal studies of enrolled patients in core centers in North America that constitute the Lysosomal Disease Network (LDN). We hypothesize that specific and localized neuroimaging and neuropsychological findings and their relationship will be distinct for each MPS disorder. Further, without treatment, functions will decline and structure will change over time in a predictable fashion, and will be related to locus of abnormality and stage of disease 2) to develop quantitative measurements of change; including direct measurement of neuropsychological function, surrogate MRI markers, and biomarkers to measure stage of disease and treatment outcomes. 3) to examine the degree to which independent variables ( such as age at first treatment, severity of disease, types of medical abnormalities, mutation, medical events, sensory abnormalities and others) have an impact on both functional and structural outcome brain variables as well as quality-of-life. 4) to examine how treatments such as ERT, HSCT, substrate reduction and other palliative and rehabilitation therapies differentially affect CNS structure and functions and quality of life (QOL). Methods: Over the first two years 70 children will be enrolled and followed in this study from 8 centers over five years; 30 MPS I, 20 MPS II, and 20 MPS VI. Each child will be seen yearly for a total of at least 3 or possibly 4 follow-up visits within the five year period. A quantitative neuroimaging and neuropsychological protocol will be used to collect data as well as relevant medical and environmental variables that may impact these measures. A new biomarker that may be sensitive to change will also be collected. Data will be analyzed to determine the locus of central nervous system abnormality, the sensitivity of measures to change and disease progression, and to identify the variables that contribute to these outcomes.