title: Lysosomal storage disease: gene therapy on both sides of the blood-brain barrier.
abstract: Most lysosomal storage disorders affect the nervous system as well as other tissues and organs of the body. Previously, the complexities of these diseases, particularly in treating neurologic abnormalities, were too great to surmount. However, based on recent developments there are realistic expectations that effective therapies are coming soon. Gene therapy offers the possibility of affordable, comprehensive treatment associated with these diseases currently not provided by standards of care. With a focus on correction of neurologic disease by systemic gene therapy of mucopolysaccharidoses types I and IIIA, we review some of the major recent advances in viral and non-viral vectors, methods of their delivery and strategies leading to correction of both the nervous and somatic tissues as well as evaluation of functional correction of neurologic manifestations in animal models. We discuss two questions: what systemic gene therapy strategies work best for correction of both somatic and neurologic abnormalities in a lysosomal storage disorder and is there evidence that targeting peripheral tissues (e.g., in the liver) has a future for ameliorating neurologic disease in patients?
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, United States; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, United States. Electronic address: arono001@umn.edu.
authors.forename: Elena L
authors.initials: EL
authors.lastname: Aronovich
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, United States; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, United States.
authors.forename: Perry B
authors.initials: PB
authors.lastname: Hackett
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000235:genetics* / Q000628:therapy*; D008247:Lysosomes / Q000235:genetics; D008059:Mucopolysaccharidosis I / Q000235:genetics / Q000628:therapy; D009084:Mucopolysaccharidosis III / Q000235:genetics / Q000628:therapy
keywords: Behavior; CNS; Mucopolysaccharidosis; Neurologic; Sleeping Beauty transposon; Transcytosis