title: Recent developments in therapeutic approaches for lysosomal storage diseases.
abstract: Genetic mutations that cause specific lysosomal protein deficiencies account for more than 45 Lysosomal Storage Diseases (LSDs), mostly pre-adult disorders which are associated with neurological symptoms and mental retardation. Interestingly, such diseases are often characterized by intracellular deposition and protein aggregation, events also found in age-related neurodegenerative diseases. During the past twenty years, different approaches have been introduced for the treatment of these disorders, several of which are now in routine clinical use or clinical trials. Among them, enzyme replacement therapy (ERT) represented a major progress. However, the usefulness of ERT is limited due to the fact that enzyme distribution is insufficient and treatment costs are very high. A further novel therapeutic option for LSDs is based on the use of small molecules, that can either inhibit a key enzyme which is responsible for substrate synthesis (substrate reduction) or act as a chaperone to increase the residual activity of the lysosomal enzyme (pharmacological chaperones). In addition, recently various gene therapy approaches have been developed, mostly based on adeno-associated and lentiviral vectors, and strategies based on stem cells administration are beginning their route. This review provides an update of the status of research on LSDs therapeutic approaches, including recent patents in the field.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06126 Perugia, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Urbanelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Magini
authors.forename: Alice
authors.initials: A
authors.lastname: Polchi
authors.forename: Mario
authors.initials: M
authors.lastname: Polidoro
authors.forename: Carla
authors.initials: C
authors.lastname: Emiliani
mesh_terms: D056947:Enzyme Replacement Therapy; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D008607:Intellectual Disability / Q000209:etiology / Q000235:genetics; D016464:Lysosomal Storage Diseases / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D008247:Lysosomes / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000627:therapeutic use*; D033581:Stem Cell Transplantation
chemical_list: D018832:Molecular Chaperones; D006867:Hydrolases