title: 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: Department of Molecular Biology, University of Gdańsk, Kładki 24, 80-822 Gdańsk, Poland.
authors: Joanna
authors: J
authors: Jakóbkiewicz-Banecka
authors: Ewa
authors: E
authors: Piotrowska
authors: Magdalena
authors: M
authors: Gabig-Cimińska
authors: Elżbieta
authors: E
authors: Borysiewicz
authors: Monika
authors: M
authors: Słomińska-Wojewódzka
authors: Magdalena
authors: M
authors: Narajczyk
authors: Alicja
authors: A
authors: Węgrzyn
authors: Grzegorz
authors: G
authors: Węgrzyn
mesh_terms: D000818:Animals; D015870:Gene Expression / Q000187:drug effects*; D006025:Glycosaminoglycans / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage / Q000627:therapeutic use; D008247:Lysosomes / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D009083:Mucopolysaccharidoses / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D019636:Neurodegenerative Diseases / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use; D012235:Rhodamines / Q000008:administration & dosage / Q000627:therapeutic use; D013379:Substrate Specificity
chemical_list: D006025:Glycosaminoglycans; D007529:Isoflavones; D034741:RNA, Small Interfering; D012235:Rhodamines; C029773:rhodamine B