Acidic Fibroblast Growth Factor in Spinal Cord Injury: A Potential Therapy Which Merits Further Investigation

Abstract

In the current issue of Neurospine, Ko et al.1 reviewed the traumatic spinal cord injury (SCI) clinical trials completed this decade; focusing on the application of acidic fibroblast growth factor (aFGF) to promote neural regeneration. FGFs are a family of growth factors that are involved in angiogenesis, wound healing, embryonic development, and various endocrine signaling pathways.2 When applied in the setting of SCI, FGF attenuates biological processes that are associated with secondary injury such as astrocyte activation, neuroinflammation, and scar formation.3 These favorable attributes make aFGF a tempting therapeutic candidate for SCI. In a phase I study of aFGF, 9 patients with chronic cervical SCI were treated with aFGF in fibrin glue via a laminectomy, followed by booster aFGF administration at 3and 6-month postinjury. Modest nerve regeneration occurred in all patients, and 2 patients showed improvement in American Spinal Cord Injury Association (ASIA) motor scores.4 This was followed by an open label, nonrandomized, uncontrolled phase II trial in 2011 that demonstrated significant improvement in ASIA motor and sensory scores, as well as increased functional independence measures 1 year after aFGF intervention.5 Furthermore, throughout the 4-year follow-up period of the clinical trial, the authors found that aFGF administration improved functional recovery without any clinically related major adverse events.6 The aforementioned clinical reports of aFGF are meaningful because they confirm the safety of aFGF administration, including the absence of any tumorigenic episodes within the injured spinal cord. However, the readers of the review article should be aware of a pitfall when interpreting the aFGF trials with regards to the timing of patient recruitment and intervention. Notably, the timing for initiation of aFGF administration was broad: from 2.3 to 105.4 months after injury in the cervical SCI group and from 1.5 to 135.8 months after injury in the thoracolumbar group. The recruited patients in the trial were subacute or chronic SCI patients described in the article as being in a ‘relatively stable neurological status,’ which implies that the potential natural recovery during the follow-up period would be comparable among enrolled patients. The international campaign for cures of spinal cord injury paralysis (ICCP), which supports an international panel tasked with reviewing the methodology for clinical trials in SCI, states that spontaneous recovery can be observed in Neurospine 2019;16(4):739-741. https://doi.org/10.14245/ns.19edi.018 Neurospine