Longitudinal Studies of Brain Structure and Function in MPS Disorder

MPS 疾病脑结构和功能的纵向研究

• 批准号: 7884796
• 负责人: ELSA G SHAPIRO
• 金额: $ 9.58万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7884796
• 关键词: Address; Admixture; Affect; Age; Anisotropy; Attention; Behavioral; Biological; Biological Factors; Biological Markers; Brain; Brain Diseases; Central Nervous System Diseases; Child; Childhood; Clinical; Clinical Trials Network; Cognitive; Congenital neurologic anomalies; Connective Tissue Diseases; Data; Data Collection; Dementia; Deterioration; Development; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Enrollment; Environmental Risk Factor; Enzymes; Event; Functional disorder; Goals; Gray unit of radiation dose; Hematopoietic stem cells; Hippocampus (Brain); Impaired cognition; Learning; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Medical; Memory; Methods; Mucopolysaccharidoses; Mucopolysaccharidosis I; Mucopolysaccharidosis III; Mucopolysaccharidosis IV; Mucopolysaccharidosis VI; Mutation; Natural History; Nervous System Physiology; Nervous system structure; Neuraxis; Neurocognitive; Neurocognitive Deficit; Neurologic; Neuropsychological Tests; North America; Outcome; Parents; Patients; Pilot Projects; Protocols documentation; Quality of life; Rehabilitation therapy; Research; Research Personnel; Sampling; Sensory; Severity of illness; Somatotropin; Staging; Stem cell transplant; Structure; Techniques; Therapeutic; Time; Treatment outcome; Vertebral column; Visit; body system; bone; chemotherapy; cognitive function; enzyme replacement therapy; executive function; follow-up; functional decline; neurobehavioral; neuroimaging; neuropsychological; outcome forecast; palliative; psychosocial; skeletal; white matter

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.

粘多糖贮积症是溶酶体疾病，逐渐影响大多数器官系统 身体通常从童年开始。最近的治疗进展已经改善了一些症状 这些功能障碍，尤其是大脑和骨骼的功能障碍，很难治疗。这项研究解决了 MPS 疾病中的大脑异常目前知之甚少。 这项研究的目标是： 1）识别中枢神经系统（CNS）结构和功能的异常并进行测量 随着时间的推移，治疗和未治疗的 MPS 疾病患者的生活质量 (QOL)。我们将完成 这是通过对北美核心中心的入组患者进行纵向研究来实现的，这些中心构成了 溶酶体疾病网络（LDN）。我们假设特定和局部的神经影像学和 每种 MPS 疾病的神经心理学发现及其关系都是不同的。进一步地，没有 治疗后，功能会衰退，结构会随着时间的推移以可预测的方式发生变化，并且会 与异常部位和疾病阶段相关 2）制定变化的定量测量方法；包括直接测量神经心理学 功能、替代 MRI 标记和生物标记来测量疾病阶段和治疗结果。 3）检查自变量（例如首次治疗时的年龄、疾病的严重程度）的程度 疾病、医疗异常类型、突变、医疗事件、感觉异常等） 对大脑功能和结构结果变量以及生活质量的影响。 4) 检查ERT、HSCT、底物减少和其他姑息治疗等治疗方法如何 康复治疗对中枢神经系统结构和功能以及生活质量（QOL）有不同的影响。 方法：在最初的两年里，来自 8 个中心的 70 名儿童将被纳入这项研究并进行随访 五年以上； 30 MPS I、20 MPS II 和 20 MPS VI。每个孩子每年至少会见 3 次 或者五年内可能进行 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的相关医疗和环境变量 这些措施。还将收集可能对变化敏感的新生物标志物。数据将是 分析以确定中枢神经系统异常的部位、措施的敏感性 变化和疾病进展，并确定导致这些结果的变量。