Enzyme replacement therapy results in substantial improvements in early clinical phenotype in a mouse model of globoid cell leukodystrophy
| العنوان: | Enzyme replacement therapy results in substantial improvements in early clinical phenotype in a mouse model of globoid cell leukodystrophy |
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| المؤلفون: | Melody Stallings-Mann, Frederick J. Troendle, Andrew Courtenay, Michael W. DeLucia, Wing C. Lee, Chad A. Dickey, Dennis W. Dickson, Christopher B. Eckman |
| المصدر: | The FASEB Journal. 19:1549-1551 |
| بيانات النشر: | Wiley, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | medicine.medical_specialty, Central nervous system, Neurological disorder, Disease, Biology, Biochemistry, Cell Line, Mice, Internal medicine, Galactosylceramidase, Genetics, medicine, Animals, Humans, Gait, Molecular Biology, Leukodystrophy, Psychosine, Enzyme replacement therapy, medicine.disease, Immunohistochemistry, Recombinant Proteins, Failure to Thrive, Leukodystrophy, Globoid Cell, Mice, Inbred C57BL, Disease Models, Animal, Phenotype, medicine.anatomical_structure, Endocrinology, Blood-Brain Barrier, Failure to thrive, Krabbe disease, medicine.symptom, Biotechnology |
| الوصف: | Globoid cell leukodystrophy (GLD) or Krabbe disease is a devastating, degenerative neurological disorder caused by mutations in the galactosylceramidase (GALC) gene that severely affect enzyme activity. Currently, treatment options for this disorder are very limited. Enzyme replacement therapy (ERT) has been shown to be effective in lysosomal storage disorders with predominantly peripheral manifestations such as type I Gaucher's and Fabry's disease. Little however is known about the possible benefit of ERT in GLD, which has a substantial central nervous system component. In this study, we examined the effect of peripheral GALC injections in the twitcher mouse model of the disease. Although we were unable to block the precipitous decline that normally occurs just before death, we did observe significant early improvements in motor performance, a substantial attenuation in the initial failure to thrive, and an increase in life span. Immunohistochemical and activity analyses demonstrated GALC uptake in multiple tissues, including the brain. This was associated with a decrease in the abnormal accumulation of the GALC substrate psychosine, which is thought to play a pivotal role in disease pathology. These results indicate that peripheral ERT is likely to be beneficial in GLD. |
| تدمد: | 1530-6860 0892-6638 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d0eb123549ada5d53bad5a469befda1e https://doi.org/10.1096/fj.05-3826fje |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....d0eb123549ada5d53bad5a469befda1e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15306860 08926638 |
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