Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.2.1.31 (
beta-glucuronidase
)
7,680
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Most lysosomal storage diseases have central nervous system (CNS) involvement. No effective treatment is available at present. We investigated the usefulness of brain-directed gene therapy and cell therapy using mouse models of lysosomal storage diseases. For gene therapy to the CNS, a recombinant adenovirus encoding beta-galactocerebrosidase gene was injected into the cerebral ventricle of neonatal twitcher mice, a murine model of
Krabbe disease
. Improvements in neurological symptoms and a prolonged lifespan were observed. Brain activity of beta-galactocerebrosidase was increased significantly and the concentration of a cytotoxic metabolite, psychosine, was decreased. Pathological observations of the brain were also improved in treated twitcher mice. For cell therapy to the CNS, a neural stem cell line derived from human fetal brain was genetically engineered to overexpress
beta-glucuronidase
and transplanted into the cerebral ventricles of neonatal MPS VII mice, a model of beta-glucuronidase deficiency. Transplanted human neural stem cells were found to integrate and migrate in the host brain and to produce large amounts of
beta-glucuronidase
. Brain contents of the substrate of
beta-glucuronidase
were reduced and widespread clearing of lysosomal storage was observed in treated MPS VII mice. These data suggest that brain-directed gene/cell therapy may be useful in the treatment of neurological alterations in lysosomal storage diseases.
...
PMID:Treatment of lysosomal storage disorders: cell therapy and gene therapy. 1519 Jan 97
