Reversal of peripheral and central neural storage and ataxia after recombinant enzyme replacement therapy in α-mannosidosis mice
| Autor: | Stijn Stroobants, Paul Saftig, Renate Lüllmann-Rauch, Claes Andersson, Rudi D'Hooge, Meike Lüdemann, Jens Fogh, Willy Morelle, Judith Blanz, Helena Reuterwall, Jean Claude Michalski |
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| Rok vydání: | 2008 |
| Předmět: |
Nervous system
medicine.medical_specialty Alpha-mannosidosis Biology Kidney Blood–brain barrier Hippocampus Receptor IGF Type 2 Mannosidosis Mice Trigeminal ganglion alpha-Mannosidase Internal medicine Genetics medicine Animals Humans Molecular Biology Genetics (clinical) Neurons Mannose 6-phosphate receptor Brain General Medicine Enzyme replacement therapy medicine.disease Recombinant Proteins Metachromatic leukodystrophy Disease Models Animal medicine.anatomical_structure Endocrinology Liver Trigeminal Ganglion Blood-Brain Barrier Vacuoles alpha-Mannosidosis Ataxia Lysosomes Spleen |
| Zdroj: | Human Molecular Genetics. 17:3437-3445 |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddn237 |
| Popis: | Despite the progress in the treatment of lysosomal storage disorders (LSDs) mainly by enzyme replacement therapy, only limited success was reported in targeting the appropriate lysosomal enzyme into the brain. This prevents efficient clearance of neuronal storage, which is present in many of these disorders including alpha-mannosidosis. Here we show that the neuropathology of a mouse model for alpha-mannosidosis can be efficiently treated using recombinant human alpha-mannosidase (rhLAMAN). After intravenous administration of different doses (25-500 U/kg), rhLAMAN was widely distributed among tissues, and immunohistochemistry revealed lysosomal delivery of the injected enzyme. Whereas low doses (25 U/kg) led to a significant clearance ( |
| Databáze: | OpenAIRE |
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