Linked Life Data

12556220

Source:http://linkedlifedata.com/resource/pubmed/id/12556220

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-1-30
pubmed:abstractText
Gaucher disease (GD) is an inborn error of glycosphingolipid metabolism, associated with multisystemic manifestations resulting from the lysosomal accumulation of an incompletely degraded material (glucosylceramide) within cells of monocyte/macrophage lineage. In the majority of GD patients with non-neurological involvement (type 1), the clinical features are dominated by haematological, visceral (hepatic and splenic) and skeletal complications. Infrequently, cardiopulmonary involvement may develop and lead to major morbidity. Investigations of substrate turnover within cellular compartments, such as the lysosome, indicate that progressive tissue storage occurs when the activity of the responsible hydrolytic enzyme declines. Thus, the provision of functional enzyme to deficient cells is a straightforward means of achieving metabolic correction. Conversely, the concentration of stored substrate within cells bearing particular affected enzymes (i.e., expressing residual activity) may be controlled by a reduction of the 'load'. This means that metabolic homeostasis can also be restored by restricting the amount of substrate presented to disease cells to a level that can be hydrolysed by the existing enzyme activity. Proof-of-concept for both approaches has been demonstrated through enzyme replacement therapy using alglucerase/imiglucerase and more recently, substrate reduction therapy by miglustat. Enzyme replacement therapy is proven to be safe and effective in the treatment of GD type 1, establishing imiglucerase as the current standard of care. The experience with substrate reduction therapy, specifically miglustat, is limited but encouraging. This review is an attempt to examine the potential role of this latter approach in light of current patient management. The consideration of miglustat as a therapeutic option requires the appropriate selection of patients (amongst those unwilling or unsuitable to receive enzyme replacement therapy), a definition of the therapeutic objectives and monitoring not only for response but potential adverse effects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1354-3784
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
273-81
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Substrate reduction therapy: miglustat as a remedy for symptomatic patients with Gaucher disease type 1.
pubmed:affiliation
Neurogenetics Unit, Department of Neurology and Pediatrics, New York University School of Medicine, New York, USA. gregory.pastores@med.nyu.edu
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't