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

Abstract

The present study investigated cerebrospinal fluid (CSF) biomarkers for estimating degeneration of the central nervous system (CNS) in experimental dogs with GM1 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 beta-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.

• Authors: Hiroyuki Satoh, Osamu Yamato, Tomoya Asano, Madoka Yonemura, Toyofumi Yamauchi, Daisuke Hasegawa, Hiromitsu Orima, Toshiro Arai, Masahiro Yamasaki, Yoshimitsu Maede
• Journal: Brain research (Brain Res) Vol. 1133 Issue 1 Pg. 200-8 (Feb 16 2007) ISSN: 0006-8993 [Print] Netherlands
• PMID: 17196562 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Biomarkers
• Cerebrospinal Fluid Proteins
• Myelin Basic Protein
• G(M1) Ganglioside
• Prednisolone
• L-Lactate Dehydrogenase
• Aspartate Aminotransferases
• Phosphopyruvate Hydratase

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Aspartate Aminotransferases (analysis, cerebrospinal fluid)
• Biomarkers (analysis, cerebrospinal fluid)
• Brain (metabolism, physiopathology)
• Cerebrospinal Fluid Proteins (cerebrospinal fluid)
• Disease Models, Animal
• Dogs
• G(M1) Ganglioside (analysis, cerebrospinal fluid)
• Gangliosidosis, GM1 (cerebrospinal fluid, diagnosis, drug therapy)
• L-Lactate Dehydrogenase (analysis, cerebrospinal fluid)
• Myelin Basic Protein (analysis, cerebrospinal fluid)
• Nerve Degeneration (cerebrospinal fluid, diagnosis, drug therapy)
• Phosphopyruvate Hydratase (analysis, cerebrospinal fluid)
• Predictive Value of Tests
• Prednisolone (therapeutic use)
• Treatment Outcome
• Up-Regulation (physiology)