title: Gene therapy for neurologic manifestations of mucopolysaccharidoses.
abstract: BACKGROUND
  Mucopolysaccharidoses (MPS) are a family of lysosomal disorders caused by mutations in genes that encode enzymes involved in the catabolism of glycoaminoglycans. These mutations affect multiple organ systems and can be particularly deleterious to the nervous system. At the present time, enzyme replacement therapy and hematopoietic stem-cell therapy are used to treat patients with different forms of these disorders. However, to a great extent, the nervous system is not adequately responsive to current therapeutic approaches.
  
  
  METHODS
  Recent advances in gene therapy show great promise for treating MPS. This article reviews the current state of the art for routes of delivery in developing genetic therapies for treating the neurologic manifestations of MPS.
  
  
  CONCLUSIONS
  Gene therapy for treating neurological manifestations of MPS can be achieved by intraventricular, intrathecal, intranasal and systemic administrations. The intraventricular route of administration appears to provide the most widespread distribution of gene therapy vectors to the brain. The intrathecal route of delivery results in predominant distribution to the caudal areas of the brain. The systemic route of delivery via intravenous infusion can also achieve widespread delivery to the CNS; however, the distribution to the brain is greatly dependent on the vector system. Intravenous delivery using lentiviral vectors appear to be less effective than adeno-associated viral (AAV) vectors. Moreover, some subtypes of AAV vectors are more effective than others in crossing the blood-brain barrier. In summary, the recent advances in gene vector technology and routes of delivery to the CNS will facilitate the clinical translation of gene therapy for the treatment of the neurological manifestations of MPS.
authors.affiliation: University of Minnesota, Department of Genetics, Cell Biology, and Development , Minneapolis, MN 55455 , USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Wolf
authors.forename: Sharbani
authors.initials: S
authors.lastname: Banerjee
authors.forename: Perry B
authors.initials: PB
authors.lastname: Hackett
authors.forename: Chester B
authors.initials: CB
authors.lastname: Whitley
authors.forename: R Scott
authors.initials: RS
authors.lastname: McIvor
authors.forename: Walter C
authors.initials: WC
authors.lastname: Low
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D056947:Enzyme Replacement Therapy / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D009083:Mucopolysaccharidoses / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*
keywords: Hunter syndrome; Hurler syndrome; Sanfilippo syndrome; enzyme replacement therapy; gene therapy