title: Emerging drugs for the treatment of mucopolysaccharidoses.
abstract: BACKGROUND
  Despite being reported for the first time almost one century ago, only in the last few decades effective have treatments become available for the mucopolysaccharidoses (MPSs), a group of 11 inherited metabolic diseases that affect lysosomal function. These diseases are progressive, usually severe, and, in a significant number of cases, involve cognitive impairment.
  
  
  METHODS
  This review will not cover established treatments such as bone marrow/hematopoietic stem cell transplantation and classic intravenous enzyme replacement therapy (ERT), whose long-term outcomes have already been published (MPS I, MPS II, and MPS VI), but it instead focuses on emerging therapies for MPSs. That includes intravenous ERT for MPS IVA and VII, intrathecal ERT, ERT with fusion proteins, substrate reduction therapy, gene therapy, and other novel approaches.
  
  
  CONCLUSIONS
  The available treatments have resulted in improvements for several disease manifestations, but they still do not represent a cure for these diseases; thus, it is important to develop alternative methods to approach the unmet needs (i.e. bone disease, heart valve disease, corneal opacity, and central nervous system (CNS) involvement). The work in progress with novel approaches makes us confident that in 2017, when MPS will commemorate 100 years of its first report, we will be much closer to an effective cure for these challenging conditions.
authors.affiliation: a Medical Genetics Service and Clinical Research Group in Medical Genetics , Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil.|b Department of Genetics , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.|c Post-Graduate Program in Child and Adolescent Health , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.|d Post-Graduate Program in Genetics and Molecular Biology , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.affiliation: a Medical Genetics Service and Clinical Research Group in Medical Genetics , Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil.|c Post-Graduate Program in Child and Adolescent Health , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.
authors.forename: Andressa
authors.initials: A
authors.lastname: Federhen
authors.affiliation: a Medical Genetics Service and Clinical Research Group in Medical Genetics , Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil.
authors.forename: Filippo
authors.initials: F
authors.lastname: Vairo
authors.affiliation: a Medical Genetics Service and Clinical Research Group in Medical Genetics , Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil.|e Post-Graduate Program in Biological Sciences: Biochemistry , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Vanzella
authors.affiliation: a Medical Genetics Service and Clinical Research Group in Medical Genetics , Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil.|b Department of Genetics , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Pasqualim
authors.affiliation: a Medical Genetics Service and Clinical Research Group in Medical Genetics , Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil.
authors.forename: Letícia Machado Rosa
authors.initials: LM
authors.lastname: da Silva
authors.affiliation: a Medical Genetics Service and Clinical Research Group in Medical Genetics , Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Giugliani
authors.affiliation: a Medical Genetics Service and Clinical Research Group in Medical Genetics , Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil.
authors.forename: Ana Paula Kurz
authors.initials: AP
authors.lastname: de Boer
authors.affiliation: a Medical Genetics Service and Clinical Research Group in Medical Genetics , Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil.
authors.forename: Carolina Fishinger Moura
authors.initials: CF
authors.lastname: de Souza
authors.affiliation: b Department of Genetics , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.|d Post-Graduate Program in Genetics and Molecular Biology , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.|f Gene Therapy Center , Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil.
authors.forename: Ursula
authors.initials: U
authors.lastname: Matte
authors.affiliation: d Post-Graduate Program in Genetics and Molecular Biology , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.|f Gene Therapy Center , Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil.|g Department of Physiology , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Baldo
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000209:etiology / Q000628:therapy*; D018450:Disease Progression; D015195:Drug Design; D056947:Enzyme Replacement Therapy / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D009083:Mucopolysaccharidoses / Q000150:complications / Q000503:physiopathology / Q000628:therapy*
keywords: Mucopolysaccharidoses; emerging treatments; enzyme replacement therapy; gene therapy; glycosaminoglycans; lysosomal storage diseases