title: Gene therapy for metachromatic leukodystrophy.
abstract: Leukodystrophies (LDs) are rare, often devastating genetic disorders with neurologic symptoms. There are currently no disease-specific therapeutic approaches for these diseases. In this review we use metachromatic leukodystrophy as an example to outline in the brief the therapeutic approaches to MLD that have been tested in animal models and in clinical trials, such as enzyme-replacement therapy, bone marrow/umbilical cord blood transplants, ex vivo transplantation of genetically modified hematopoietic stem cells, and gene therapy. These studies suggest that to be successful the ideal therapy for MLD must provide persistent and high level expression of the deficient gene, arylsulfatase A in the CNS. Gene therapy using adeno-associated viruses is therefore the ideal choice for clinical development as it provides the best balance of potential for efficacy with reduced safety risk. Here we have summarized the published preclinical data from our group and from others that support the use of a gene therapy with AAVrh.10 serotype for clinical development as a treatment for MLD, and as an example of the potential of gene therapy for LDs especially for Krabbe disease, which is the focus of this special issue. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Rosenberg
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Kaminsky
authors.affiliation: INSERM U1169, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Aubourg
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York. geneticmedicine@med.cornell.edu.
authors.forename: Dolan
authors.initials: D
authors.lastname: Sondhi
mesh_terms: D000818:Animals; D002553:Cerebroside-Sulfatase / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007966:Leukodystrophy, Metachromatic / Q000235:genetics / Q000628:therapy*
chemical_list: D002553:Cerebroside-Sulfatase
keywords: adeno-associated virus; clinical development; clinical translation; gene therapy; metachromatic leukodystrophy