title: Intrathecal injection of a therapeutic gene-containing polyplex to treat spinal cord injury.
abstract: Spinal cord injury (SCI) is a serious clinical problem that suddenly deprives patients of neurologic function and drastically diminishes their quality of life. Gene introduction has the potential to be effective for various pathological states of SCI because various proteins can be produced just by modifying nucleic acid sequences. In addition, the sustainable protein expression allows to maintain its concentration at an effective level at the target site in the spinal cord. Here we propose an approach using a polyplex system composed of plasmid DNA (pDNA) and a cationic polymer, poly{N'-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} [PAsp(DET)], that has high capacity to promote endosome escape and the long-term safety by self-catalytically degrading within a few days. We applied brain-derived neurotrophic factor (BDNF)-expressing pDNA for SCI treatment by intrathecal injection of PAsp(DET)/pDNA polyplex. A single administration of polyplex for experimental SCI provided sufficient therapeutic effects including prevention of neural cell death and enhancement of motor function recovery. This lasted for a few weeks after SCI, demonstrating the capability of this system to express BDNF in a safe and responsible manner for treatment of various pathological states in SCI.
authors.affiliation: Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for the Persons with Disabilities, Saitama, Japan; Sensory and Motor System Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hayakawa
authors.affiliation: Laboratory of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uchida
authors.affiliation: Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for the Persons with Disabilities, Saitama, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Ogata
authors.affiliation: Sensory and Motor System Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Sakae
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Laboratory of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan. Electronic address: kataoka@bmw.t.u-tokyo.ac.jp.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
authors.affiliation: Sensory and Motor System Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Laboratory of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: itaka-ort@umin.net.
authors.forename: Keiji
authors.initials: K
authors.lastname: Itaka
mesh_terms: D000818:Animals; D017209:Apoptosis; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016207:Cytokines / Q000235:genetics; D004247:DNA / Q000008:administration & dosage*; D005260:Female; D018014:Gene Transfer Techniques; D007278:Injections, Spinal; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000008:administration & dosage*; D010957:Plasmids; D011108:Polymers / Q000008:administration & dosage*; D013119:Spinal Cord Injuries / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; C539404:PAsp(DET); D010455:Peptides; D011108:Polymers; D004247:DNA
keywords: Brain-derived neurotrophic factor (BDNF); Gene delivery; Intrathecal injection; Polyplex; Spinal cord injury