Cerebrospinal fluid biomarkers showing neurodegeneration in dogs with GM1 gangliosidosis: Possible use for assessment of a therapeutic regimen

Abstract

gangliosidosis and preliminarily evaluated the efficacy of long-term glucocorticoid therapy for GM1 gangliosidosis using the biomarkers identified here. GM1 gangliosidosis, a lysosomal storage disease that affects the brain and multiple systemic organs, is due to an autosomal recessively inherited deficiency of acid β-galactosidase activity. Pathogenesis of GM1 gangliosidosis may include neuronal apoptosis and abnormal axoplasmic transport and inflammatory response, which are perhaps consequent to massive neuronal storage of GM1 ganglioside. In the present study, we assessed some possible CSF biomarkers, such as GM1 ganglioside, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), neuron-specific enolase (NSE) and myelin basic protein (MBP). Periodic studies demonstrated that GM1 ganglioside concentration, activities of AST and LDH, and concentrations of NSE and MBP in CSF were significantly higher in dogs with GM1 gangliosidosis than those in control dogs, and their changes were well related with the months of age and clinical course. In conclusion, GM1 ganglioside, AST, LDH, NSE and MBP could be utilized as CSF biomarkers showing CNS degeneration in dogs with GM1 gangliosidosis to evaluate the efficacy of novel therapies proposed for this disease. In addition, we preliminarily treated an affected dog with long-term oral administration of prednisolone and evaluated the efficacy of this therapeutic trial using CSF biomarkers determined in the present study. However, this treatment did not change either the clinical course or the CSF biomarkers of the affected dog, suggesting that glucocorticoid therapy would not be effective for treating GM1 gangliosidosis.3

Proteome Analysis of Cerebrospinal Fluid in Healthy Beagles and Canine Encephalitis

“…In humans, there is evidence that the NSE concentration in the CSF rises with age [18]. In the previous report, the dogs were 1-13 months old [14]. In the present study, the age of the healthy dogs was 2-9 years old with an average age of 4.9 ± 2.8 years old.…”

“…However, many of the proteins in canine CSF that we identified after centrifugal filter desalting have been identified in 2DE studies in humans and other animals [2,7,8]. Neuron-specific enolase (NSE) is known as a biomarker of CNS disorders, for example, ischemia, head trauma, spinal cord injury and some of tumors, in humans [3, 6, 9, 12, In present study, the concentration of NSE of healthy dogs was higher than that found in a previous report [14]. This is likely due to the difference in methodology and age of the control group.…”

“…Because NSE is usually present in a nerve cell, it is possible that NSE leaked as a result of neuronal destruction. In previous report, even GM1 gangliosidosis increased, so an increasing NSE level may not be specific in encephalitis [14]. Also, we used only beagles as a healthy dog group in this study.…”

Associations between cerebrospinal fluid biomarkers and long-term neurologic outcome in dogs with acute intervertebral disk herniation

“…Other researchers have not found CSF CK activity to be a useful determinant of disease status or outcome in humans 17 or horses. 18 In humans with head trauma, 19 CSF AST activity has been associated with lesion severity, and in dogs, 20 it has been detected in individuals with degenerative diseases of the CNS.…”

The chaperone protein clusterin may serve as a cerebrospinal fluid biomarker for chronic spinal cord disorders in the dog

“…Cerebrospinal fluid (CSF) has been investigated as a potential source of biomarkers in a range of human and animal neurological disorders (Satoh et al 2007;Tumani et al 2008). From a veterinary perspective, a number of neurological conditions can present similar clinical features and therefore the identification of specific biomarkers would greatly facilitate diagnosis, patient treatment and management strategies.…”