title: Gene therapy approaches in the non-human primate model of Parkinson's disease.
abstract: The field of gene therapy has recently witnessed a number of major conceptual changes. Besides the traditional thinking that comprises the use of viral vectors for the delivery of a given therapeutic gene, a number of original approaches have been recently envisaged, focused on using vectors carrying genes to further modify basal ganglia circuits of interest. It is expected that these approaches will ultimately induce a therapeutic potential being sustained by gene-induced changes in brain circuits. Among others, at present, it is technically feasible to use viral vectors to (1) achieve a controlled release of neurotrophic factors, (2) conduct either a transient or permanent silencing of any given basal ganglia circuit of interest, (3) perform an in vivo cellular reprogramming by promoting the conversion of resident cells into dopaminergic-like neurons, and (4) improving levodopa efficacy over time by targeting aromatic L-amino acid decarboxylase. Furthermore, extensive research efforts based on viral vectors are currently ongoing in an attempt to better replicate the dopaminergic neurodegeneration phenomena inherent to the progressive intraneuronal aggregation of alpha-synuclein. Finally, a number of incoming strategies will soon emerge over the horizon, these being sustained by the underlying goal of promoting alpha-synuclein clearance, such as, for instance, gene therapy initiatives based on increasing the activity of glucocerebrosidase. To provide adequate proof-of-concept on safety and efficacy and to push forward true translational initiatives based on these different types of gene therapies before entering into clinical trials, the use of non-human primate models undoubtedly plays an instrumental role.
authors.affiliation: Department of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra, Pio XII Ave 55, Edificio CIMA, 31008, Pamplona, Navarra, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.|Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Pignataro
authors.affiliation: Department of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra, Pio XII Ave 55, Edificio CIMA, 31008, Pamplona, Navarra, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.|Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Sucunza
authors.affiliation: Department of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra, Pio XII Ave 55, Edificio CIMA, 31008, Pamplona, Navarra, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.|Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
authors.forename: A J
authors.initials: AJ
authors.lastname: Rico
authors.affiliation: Department of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra, Pio XII Ave 55, Edificio CIMA, 31008, Pamplona, Navarra, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.|Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
authors.forename: I G
authors.initials: IG
authors.lastname: Dopeso-Reyes
authors.affiliation: Department of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra, Pio XII Ave 55, Edificio CIMA, 31008, Pamplona, Navarra, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.|Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Roda
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.|Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: A I
authors.initials: AI
authors.lastname: Rodríguez-Perez
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.|Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Labandeira-Garcia
authors.affiliation: Division of Neuroscience, Ospedale San Raffaele, 20132, Milan, Italy.|CNR Institute of Neuroscience, 20129, Milan, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Broccoli
authors.affiliation: Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.affiliation: Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra, Pio XII Ave 55, Edificio CIMA, 31008, Pamplona, Navarra, Spain. jlanciego@unav.es.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. jlanciego@unav.es.|Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain. jlanciego@unav.es.
authors.forename: José L
authors.identifier: 0000-0003-2301-5419
authors.initials: JL
authors.lastname: Lanciego
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005822:Genetic Vectors; D010300:Parkinson Disease / Q000235:genetics / Q000628:therapy*; D011323:Primates; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D051844:alpha-Synuclein
keywords: Basal ganglia; Dopamine; Dyskinesia; Macaques; Neurodegeneration; Viral vectors