Distribution of acid sphingomyelinase in rodent and non-human primate brain after intracerebroventricular infusion
| Autor: | Christopher M. Treleaven, Robin J. Ziegler, Ernesto A. Salegio, Krystof S. Bankiewicz, John Bringas, Thomas J. Tamsett, Massimo S. Fiandaca, Scott D. Bercury, James Dodge, Piotr Hadaczek, Lamya S. Shihabuddin, Ronald K. Scheule |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Central nervous system Pharmacology Rats Sprague-Dawley Lateral ventricles Cerebrospinal fluid Developmental Neuroscience Parenchyma Glial cell line-derived neurotrophic factor medicine Animals Distribution (pharmacology) chemistry.chemical_classification biology Brain Macaca mulatta Recombinant Proteins Rats Infusions Intraventricular Sphingomyelin Phosphodiesterase Enzyme medicine.anatomical_structure Neurology chemistry Immunology biology.protein Female Acid sphingomyelinase medicine.drug |
| Zdroj: | Experimental Neurology. 231:261-271 |
| ISSN: | 0014-4886 |
| Popis: | One treatment approach for lysosomal storage diseases (LSDs) is the systemic infusion of recombinant enzyme. Although this enzyme replacement is therapeutic for the viscera, many LSDs have central nervous system (CNS) components that are not adequately treated by systemic enzyme infusion. Direct intracerebroventricular (ICV) infusion of a high concentration of recombinant human acid sphingomyelinase (rhASM) into the CNS over a prolonged time frame (hours) has shown therapeutic efficacy in a mouse model of Niemann–Pick A (NP/A) disease. To evaluate whether such an approach would translate to a larger brain, rhASM was infused into the lateral ventricles of both rats and Rhesus macaques, and the resulting distribution of enzyme characterized qualitatively and quantitatively. In both species, ICV infusion of rhASM resulted in parenchymal distribution of enzyme at levels that were therapeutic in the NP/A mouse model. Enzyme distribution was global in nature and exhibited a relatively steep gradient from the cerebrospinal fluid compartment to the inner parenchyma. Additional optimization of an ICV delivery approach may provide a therapeutic option for LSDs with neurologic involvement. |
| Databáze: | OpenAIRE |
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