title: Substrate deprivation therapy: a new hope for patients suffering from neuronopathic forms of inherited lysosomal storage diseases.
abstract: Lysosomal storage diseases are a group of disorders caused by defects in enzymes responsible for degradation of particular compounds in lysosomes. In most cases, these diseases are fatal, and until recently no treatment was available. Introduction of enzyme replacement therapy was a breakthrough in the treatment of some of the diseases. However, while this therapy is effective in reduction of many somatic symptoms, its efficacy in the treatment of the central nervous system is negligible, if any, mainly because of problems with crossing the blood-brain-barrier by intravenously administered enzyme molecules. On the other hand, there are many lysosomal storage diseases in which the central nervous system is affected. Results of very recent studies indicate that in at least some cases, another type of therapy, called substrate deprivation therapy (or substrate reduction therapy) may be effective in the treatment of neuronopathic forms of lysosomal storage diseases. This therapy, based on inhibition of synthesis of the compounds that cannot be degraded in cells of the patients, has been shown to be effective in several animal models of various diseases, and recent reports demonstrate its efficacy in the treatment of patients suffering from Niemann-Pick C disease and Sanfilippo disease.
authors.affiliation: Department of Molecular Biology, University of Gdansk, Kładki 24, 80-822 Gdańsk, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Jakóbkiewicz-Banecka
authors.forename: Alicja
authors.initials: A
authors.lastname: Wegrzyn
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Wegrzyn
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005776:Gaucher Disease / Q000188:drug therapy; D019833:Genistein / Q000627:therapeutic use; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000628:therapy; D008247:Lysosomes / Q000378:metabolism; D009084:Mucopolysaccharidosis III / Q000188:drug therapy*; D009542:Niemann-Pick Diseases / Q000188:drug therapy*; D012497:Sandhoff Disease / Q000188:drug therapy; D013661:Tay-Sachs Disease / Q000188:drug therapy
chemical_list: D004791:Enzyme Inhibitors; D017485:1-Deoxynojirimycin; C059896:miglustat; D019833:Genistein