Enhancement of Motor Function Recovery after Spinal Cord Injury in Mice by Delivery of Brain-Derived Neurotrophic Factor mRNA

Samuel T. Crowley; Yuta Fukushima; Satoshi Uchida; Kazunori Kataoka; Keiji Itaka

Molecular Therapy: Nucleic Acids (Sep 2019)

Enhancement of Motor Function Recovery after Spinal Cord Injury in Mice by Delivery of Brain-Derived Neurotrophic Factor mRNA

Samuel T. Crowley,
Yuta Fukushima,
Satoshi Uchida,
Kazunori Kataoka,
Keiji Itaka

Affiliations

Samuel T. Crowley: Department of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 2-3-10 Kanda-Surugadai, Chiyoda-Ku, Tokyo 101-0062, Japan; Innovation Center of Nanomedicine (iCONM), Kawasaki Institute of Industrial Promotion, 3-25-14 Tonomachi, Kawasaki-Ku, Kawasaki-Shi 210-0821, Japan
Yuta Fukushima: Department of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 2-3-10 Kanda-Surugadai, Chiyoda-Ku, Tokyo 101-0062, Japan
Satoshi Uchida: Innovation Center of Nanomedicine (iCONM), Kawasaki Institute of Industrial Promotion, 3-25-14 Tonomachi, Kawasaki-Ku, Kawasaki-Shi 210-0821, Japan; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan
Kazunori Kataoka: Innovation Center of Nanomedicine (iCONM), Kawasaki Institute of Industrial Promotion, 3-25-14 Tonomachi, Kawasaki-Ku, Kawasaki-Shi 210-0821, Japan; Policy Alternatives Research Institute, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Keiji Itaka: Department of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 2-3-10 Kanda-Surugadai, Chiyoda-Ku, Tokyo 101-0062, Japan; Innovation Center of Nanomedicine (iCONM), Kawasaki Institute of Industrial Promotion, 3-25-14 Tonomachi, Kawasaki-Ku, Kawasaki-Shi 210-0821, Japan; Corresponding author: Keiji Itaka, Department of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.

Journal volume & issue: Vol. 17
pp. 465 – 476

Abstract

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Spinal cord injury (SCI) is a debilitating condition that can cause impaired motor function or full paralysis. In the days to weeks following the initial mechanical injury to the spinal cord, inflammation and apoptosis can cause additional damage to the injured tissues. This secondary injury impairs recovery. Brain-derived neurotrophic factor is a secreted protein that has been shown to improve a variety of neurological conditions, including SCI, by promoting neuron survival and synaptic plasticity. This study treated a mouse model of contusion SCI using a single dose of brain-derived neurotrophic factor (BDNF) mRNA nanomicelles prepared with polyethylene glycol polyamino acid block copolymer directly injected into the injured tissue. BDNF levels in the injured spinal cord tissue were approximately doubled by mRNA treatment. Motor function was monitored using the Basso Mouse Scale and Noldus CatWalk Automated Gait Analysis System for 6 weeks post-injury. BDNF-treated mice showed improved motor function recovery, demonstrating the feasibility of mRNA delivery to treat SCI.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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