Substrate reduction therapy for lysosomal storage diseases.
Acta Paediatr Suppl
; 94(447): 69-75; discussion 57, 2005 Mar.
Article
en En
| MEDLINE
| ID: mdl-15895716
ABSTRACT
UNLABELLED The treatment of disordered lipoprotein metabolism with the statin class of drugs is one of the most striking successes in the field of applied medical science here the use of selective inhibitors of the first committed step of cholesterol biosynthesis, in a complex and highly regulated pathway, leads to improved outcome from a common lipid storage disease that is a blight on whole populations--atherosclerosis. By the same token, substrate reduction is an emerging therapeutic strategy for the arcane field of the lysosomal storage diseases (LSDs). Reduced biosynthesis of glucosylceramide is postulated to allow correction of the imbalance between formation and breakdown of glycosphingolipids; the therapeutic effect of substrate reduction depends upon the presence of residual hydrolytic activity towards those accumulated glycosphingolipid substrates derived from glucosylceramide. First pioneered in the laboratory by Norman Radin, this approach has now been introduced into the clinic based on the ability to inhibit uridine diphosphate glucosylceramide transferase, the semi-selective iminosugar, N-butyldeoxynojirimycin, is licensed for the treatment of type 1 Gaucher disease. CONCLUSION:
Inhibition of substrate formation has wide application in the treatment of LSDs. Decreased glucosylceramide biosynthesis has therapeutic potential in glycosphingolipidoses other than Gaucher disease, and offers promise in several neurodegenerative storage disorders that are currently beyond the reach of other procedures. The results of ongoing clinical trials of miglustat in type 3 Gaucher disease, Niemann-Pick disease type C and GM2 gangliosidosis are eagerly awaited.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades por Almacenamiento Lisosomal
/
1-Desoxinojirimicina
/
Inhibidores Enzimáticos
Límite:
Humans
Idioma:
En
Revista:
Acta Paediatr Suppl
Año:
2005
Tipo del documento:
Article
País de afiliación:
Reino Unido