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Neuroprotective therapy using granulocyte colony-stimulating factor for acute spinal cord injury: a phase I/IIa clinical trial

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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.

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Acknowledgments

This work was supported by a Health Labour Science Research Grant of Japan.

Conflict of interest

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Authors and Affiliations

  1. Spine Section, Department of Orthopaedic Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan

    Hiroshi Takahashi, Masashi Yamazaki, Akihiko Okawa, Tsuyoshi Sakuma, Kei Kato, Mitsuhiro Hashimoto, Koichi Hayashi, Takeo Furuya, Takayuki Fujiyoshi, Junko Kawabe, Tomonori Yamauchi, Chikato Mannoji, Tomohiro Miyashita, Ryo Kadota, Masayuki Hashimoto, Kazuhisa Takahashi & Masao Koda

  2. Department of Orthopaedic Surgery, Kobe Red Cross Hospital, Kobe, Japan

    Yasuo Ito

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  1. Hiroshi Takahashi
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  2. Masashi Yamazaki
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Corresponding author

Correspondence to Masashi Yamazaki.

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Takahashi, H., Yamazaki, M., Okawa, A. et al. Neuroprotective therapy using granulocyte colony-stimulating factor for acute spinal cord injury: a phase I/IIa clinical trial. Eur Spine J 21, 2580–2587 (2012). https://doi.org/10.1007/s00586-012-2213-3

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  • DOI: https://doi.org/10.1007/s00586-012-2213-3

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