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. Conclusion: 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. © 2012 Springer-Verlag.