title: Neuroprotective therapy using granulocyte colony-stimulating factor for acute spinal cord injury: a phase I/IIa clinical trial.
abstract: OBJECTIVE
  Granulocyte colony-stimulating factor (G-CSF) is a cytokine that is clinically used to treat neutropenia. G-CSF also has non-hematopoietic functions and could potentially be used to treat neuronal injury. To confirm the safety and feasibility of G-CSF administration for acute spinal cord injury (SCI), we have initiated a phase I/IIa clinical trial of neuroprotective therapy using G-CSF.
  
  
  METHODS
  The trial included a total of 16 SCI patients within 48 h of onset. In the first step, G-CSF (5 μg/kg/day) was intravenously administered for 5 consecutive days to 5 patients. In the second step, G-CSF (10 μg/kg/day) was similarly administered to 11 patients. We evaluated motor and sensory functions of patients using the American Spinal Cord Injury Association (ASIA) score and ASIA impairment scale (AIS) grade.
  
  
  RESULTS
  In all 16 patients, neurological improvement was obtained after G-CSF administration. AIS grade increased by one step in 9 of 16 patients. A significant increase in ASIA motor scores was detected 1 day after injection (P < 0.01), and both light touch and pin prick scores improved 2 days after injection (P < 0.05) in the 10 μg group. No severe adverse effects were observed after G-CSF injection.
  
  
  CONCLUSIONS
  These results indicate that intravenous administration of G-CSF (10 μg/kg/day) for 5 days is essentially safe, and suggest that some neurological recovery may occur in most patients. We suggest that G-CSF administration could be therapeutic for patients with acute SCI.
authors.affiliation: Spine Section, Department of Orthopaedic Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sakuma
authors.forename: Kei
authors.initials: K
authors.lastname: Kato
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Hayashi
authors.forename: Takeo
authors.initials: T
authors.lastname: Furuya
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fujiyoshi
authors.forename: Junko
authors.initials: J
authors.lastname: Kawabe
authors.forename: Tomonori
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Chikato
authors.initials: C
authors.lastname: Mannoji
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Miyashita
authors.forename: Ryo
authors.initials: R
authors.lastname: Kadota
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ito
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.forename: Masao
authors.initials: M
authors.lastname: Koda
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy*
chemical_list: D018696:Neuroprotective Agents; D016179:Granulocyte Colony-Stimulating Factor