Natural History of Glycosphingolipid Storage Disorders

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications & trials

Abstract

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.