Natural History of Glycosphingolipid Storage Disorders

我们实验室以前的工作确定，在Sandhoff小鼠中，CNS中的无情炎症反应先于症状的发作，Sandhoff小鼠是婴儿Tay-Sachs和Sandhoff病的真实模型。 具体而言，我们发现包括TNF-α、IL-1b和MIP 1-a在内的炎性蛋白先于神经元凋亡和临床衰退的发生。 另外，长期以来已知GM 1或GM 2神经节苷脂分别在GM 1和GM 2神经节苷脂沉积症患者的脑实质中的积累是这些疾病的标志 我们目前正在进行一项自然史研究（方案02-DK-0107，糖脂贮积症中神经变性的研究），以研究GSL贮积症儿童CNS中炎性蛋白的表达和定量GM 1和GM 2神经节苷脂，并将其与磁共振成像和临床疾病进展评估的神经变性变化相关联。

Previous work in our laboratory determined that a relentless inflammatory response in the CNS preceded the onset of symptoms in the Sandhoff mouse, an authentic model of infantile Tay-Sachs and Sandhoff disease. Specifically we found that inflammatory proteins including TNF-a, IL-1b and MIP1-a precede the onset of neuronal apoptosis and clinical decline. In addition, the accumulation of GM1 or GM2 ganglioside in the brain parenchyma of GM1 and GM2 gangliosidosis patients, respectively, has long been known to be a hallmark of these diseases We are currently conducting a natural history study (Protocol 02-DK-0107, Investigation of Neurodegeneration in the Glycopshingolipid Storage Disorders) to investigate the expression of inflammatory proteins and quantitate GM1 and GM2 ganglioside in the CNS of children with GSL storage diseases and to correlate them with neurodegenerative changes as assessed by magnetic resonance imaging and clinical disease progression.