Substrate reduction therapies for mucopolysaccharidoses.

Abstract

Mucopolysaccharidoses (MPS) are inherited metabolic disorders, caused by mutations leading to dysfunction of one of enzymes involved in degradation of glycosaminoglycans (GAGs) in lysosomes. Due to their impaired degradation, GAGs accumulate in cells of patients, which results in dysfunction of tissues and organs, including the heart, respiratory system, bones, joints and central nervous system. Depending on the kind of deficient enzyme, 11 types and subtypes of MPS are currently recognized. Although enzyme replacement therapy has been developed for 3 types of MPS (types I, II and VI), this treatment was found to be effective only in management of somatic symptoms. Since all MPS types except IVA, IVB and VI are characterized by various problems with functioning of the central nervous system (CNS), a search for effective treatment of this system is highly desirable. Recent discoveries suggested that substrate reduction therapy may be an efficient method for treatment of MPS patients, including their CNS. In this review, different variants of this therapy will be discussed in the light of recently published reports.

• Authors: Joanna Jakóbkiewicz-Banecka, Ewa Piotrowska, Magdalena Gabig-Cimińska, Elżbieta Borysiewicz, Monika Słomińska-Wojewódzka, Magdalena Narajczyk, Alicja Węgrzyn, Grzegorz Węgrzyn
• Journal: Current pharmaceutical biotechnology (Curr Pharm Biotechnol) Vol. 12 Issue 11 Pg. 1860-5 (Nov 2011) ISSN: 1873-4316 [Electronic] Netherlands
• PMID: 21902626 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Glycosaminoglycans
• Isoflavones
• RNA, Small Interfering
• Rhodamines
• rhodamine B

Topics

• Animals
• Gene Expression (drug effects)
• Glycosaminoglycans (antagonists & inhibitors, biosynthesis)
• Humans
• Isoflavones (administration & dosage, therapeutic use)
• Lysosomes (enzymology, genetics, metabolism)
• Mucopolysaccharidoses (enzymology, genetics, therapy)
• Neurodegenerative Diseases (enzymology, genetics, therapy)
• RNA Interference
• RNA, Small Interfering (administration & dosage, genetics, therapeutic use)
• Rhodamines (administration & dosage, therapeutic use)
• Substrate Specificity