title: Therapeutic approaches for lysosomal storage diseases: a patent update.
abstract: Lysosomal Storage Diseases (LSDs) are inherited metabolic disorders caused by specific lysosomal protein deficiencies, which lead to abnormal storage of macromolecular substrates. Most LSDs are characterized by central nervous system (CNS) pathology, intracellular deposition and protein aggregation, events also found in age-related neurodegenerative diseases. Over the past two decades, a few approaches for the cure of these disorders have been approved for clinical use, i.e. enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). However, these treatments are hampered by major limitations, such as the poor biodistribution in the CNS for ERT and severe side effects for SRT. Several additional therapeutic strategies have been proposed. In particular clinical trials are ongoing based on enzyme enhancement by pharmacological chaperones, i.e. small molecule compounds able to increases the residual activity of the lysosomal enzyme, and gene therapy approaches. In addition, recent patents in the field provide evidence that many efforts are currently dedicated to i) improve the properties of enzymes used for ERT, ii) find new pharmacological chaperones without inhibitory effects on enzyme activity and iii) combine gene therapy approaches with genome editing methods.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Urbanelli
authors.forename: Krizia
authors.initials: K
authors.lastname: Sagini
authors.forename: Mario
authors.initials: M
authors.lastname: Polidoro
authors.forename: Alessandro
authors.initials: A
authors.lastname: Brozzi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Magini
authors.forename: Carla
authors.initials: C
authors.lastname: Emiliani
mesh_terms: D000818:Animals; D020536:Enzyme Activators / Q000627:therapeutic use*; D056947:Enzyme Replacement Therapy / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000188:drug therapy*; D010330:Patents as Topic
chemical_list: D020536:Enzyme Activators