[Show abstract][Hide abstract]ABSTRACT: Purpose We performed a phase I/IIa clinical trial and confirmed the safety and feasibility of granulocyte colony-stimulating factor (G-CSF) as neuroprotective therapy in patients with acute spinal cord injury (SCI). In this study, we retrospectively analyzed the clinical outcome in SCI patients treated with G-CSF and compared these results to a historical cohort of SCI patients treated with high-dose methylprednisolone sodium succinate (MPSS). Methods In the G-CSF group (n = 28), patients were treated from August 2009 to July 2012 within 48 h of the injury, and G-CSF (10 μg/kg/day) was administered intravenously for five consecutive days. In the MPSS group (n = 34), patients underwent high-dose MPSS therapy from August 2003 to July 2005 following the NASCIS II protocol. We evaluated the ASIA motor score and the AIS grade elevation between the time of treatment and 3-month follow-up and adverse events. Results The ΔASIA motor score was significantly higher in the G-CSF group than in the MPSS group (p G-CSF group had an AIS grade elevation of two steps compared to 0 % of patients in the MPSS group (p G-CSF group (8.3 %) (p Conclusions These results suggest that G-CSF administration is safe and effective, but a prospective randomized controlled clinical trial is needed to compare the efficacy of MPSS versus G-CSF treatment in patients with SCI.
[Show abstract][Hide abstract]ABSTRACT: Study Design. An open-labeled multicenter prospective non-randomized controlled clinical trialObjective. To confirm the feasibility of using granulocyte colony-stimulating factor (G-CSF) for treatment of acute spinal cord injury (SCI)Summary of Background Data. We previously reported that G-CSF promotes functional recovery after compression-induced spinal cord injury (SCI) in mice. Based on these findings, we conducted a multicenter prospective controlled clinical trial to assess the feasibility of G-CSF therapy for patients with acute SCI.Methods. The trial ran from August 2009 to March 2011, and included 41 SCI patients treated within 48 hours of onset. Informed consent was obtained from all patients. After providing consent, patients were divided into two groups. In the G-CSF group (17 patients), G-CSF (10 μg/kg/day) was intravenously administered for five consecutive days, and in the control group (24 patients), patients were similarly treated except for the G-CSF administration. We evaluated motor and sensory functions using the American Spinal Cord Injury Association (ASIA) score and ASIA impairment scale (AIS) at one week, three months, six months, and one year after onset.Results. Only two patients did not experience AIS improvement in the G-CSF group. In contrast, fifteen patients in the control group did not experience AIS improvement. In the analysis of increased ASIA motor score, a significant increase in G-CSF group was detected from one week after the administration compared to the control group. After that, some spontaneous increase of motor score was detected in control group, but the significant increase in G-CSF group was maintained until one year follow-up. Conclusion: Despite the limitation that patient selection was not randomized, the present results suggest the possibility that G-CSF administration has beneficial effects on neurological recovery in patients with acute SCI.
[Show abstract][Hide abstract]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.
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.
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.
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.