Safety of Granulocyte Colony-Stimulating Factor (G-CSF) Administration for Postrehabilitated Motor Complete Spinal Cord Injury Patients: An Open-Label, Phase I Study

Abstract

Granulocyte colony-stimulating factor (G-CSF) is a major growth factor in the activation and differentiation of granulocytes. This cytokine has been widely and safely employed in different conditions over many years. In this translational study, G-CSF is administered to 19 patients with chronic motor complete spinal cord injury, and outcomes are reported. All 19 patients received subcutaneous G-CSF (5 µg/kg per day) for 5 days and were followed for at least 6 months. The American Spinal Injury Association (ASIA) scale was used for motor and sensory assessment, and the International Association of Neurorestoratology-Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS) and the Spinal Cord Independence Measure (SCIM) III were used to assess improvements in the ability to perform basic daily tasks. At the 6-month follow-up, upper extremity motor scores improved by 10, which was statistically significant (p = 0.007), whereas there were no significant changes in lower extremity motor scores. Also, the median of light touch sensory scores improved by 5 (p = 0.001). Pinprick sensory scores significantly improved (p = 0.002). The median increment in SCIM III total score was 7 (p = 0.001). The improvements in bladder and bowel management as well as moderate distance mobility subscales were also significant (p < 0.05). Total IANR-SCIFRS scores changed from 17 to 32, which was statistically significant (p = 0.001); again the bladder and bowel management subscale improvements were statistically significant (p < 0.05). Mild side effects of the G-CSF treatment such as bone pain, rash, fever, neuropathic pain, and spasticity were noted in a few patients; all of them resolved after 1 week. Our results indicate that G-CSF administration is a safe process and is associated with neurological as well as functional improvement. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Subcutaneous granulocyte colony-stimulating factor administration for subacute traumatic spinal cord injuries, report of neurological and functional outcomes: a double-blind randomized controlled clinical trial

“…With the same rationale, we chose incomplete (AIS grade B-D) TSCIs for this study and considered subcutaneous G-CSF as a safe intervention. 6 According to our results, the greatest change in AIS grade in the G-CSF group was observed among AIS grade B and C patients. However, improvement in AIS grade D was less common than in AIS grade B or C patients.…”

“…38 Secondary injury may be an appropriate target for neuroprotective and clinical therapeutic interventions, 12,37 such as methylprednisolone sodium succinate (MPSS) and the related compound tirilazad mesylate, 4,9 nimodipine, 24 naloxone, 10 gancyclidine (N-methyl-d-aspartate antagonist), 32 and granulocyte colony-stimulating factor (G-CSF). 6,14,27,33 G-CSF has already been reported to have positive effects on the course of various neurological disorders experimentally, such as stroke, 30 Parkinson's disease, 20 Alzheimer's disease, 34 amyotrophic lateral sclerosis, 23 sciatic nerve injury, 17 partial cochlear nerve lesion, 21 traumatic brain injury, 31 and various rodent models of TSCI. 22 Multiple preclinical studies in TSCI models have suggested several mechanisms for the neurorestorative effects of G-CSF, including antiapoptotic activity, stem cell mobilization, angiogenesis, neurogenesis, and immunomodulation through specific signaling pathways.…”

“…18 G-CSF has been successfully used clinically for acute 14,33 and chronic 6,27 TSCI, as well as subacute compressive myelopathy 28,29 and stroke in humans. 25 Previously, on the basis of the available preclinical and clinical results described, we have conducted phase I, 6 phase I/IIa, 27 and phase III 7 clinical trials with promising results regarding safety, feasibility, and efficacy of G-CSF as a neuroprotective therapy in patients with chronic TSCI. In this trial, a phase II/III study, we attempt to determine the safety and verify the efficacy of subcutaneous G-CSF in comparison with placebo, for the treatment of subacute incomplete TSCI and compare neurological as well as functional outcomes between the 2 groups.…”

A Comparison between Therapeutic Effect of Granulocyte Colony-stimulating Factor and Methylprednisolone in Treatment of Patients with Acute Traumatic Spinal Cord Injury

“…The higher grades of injuries were correlated with poorer results. The article only assessed the chronic phase of injury and did not compare it with other treatment modalities (24). In a retrospective study conducted by Kamiya and colleagues in 2015, two groups of nonrandomized partial SCI treated by G-CSF and high-dose methylprednisolone followed up to three months were compared.…”

Regulation of Inflammatory Cytokines for Spinal Cord Injury Repair Through Local Delivery of Therapeutic Agents

“…Derakhshanrad et al recruited 19 patients, all of whom received G‐CSF (5 µg kg −1 day −1 ) subcutaneously for 5 days 235. Some patients showed mild side effects (rash, fever, bone pain, neuropathic pain, and spasticity) that disappeared in a week.…”