A study published in the Journal of Neurosurgery Spine has found that acidic fibroblast growth factor may have a neuroprotective effect and may create favourable conditions for axonal regeneration in patients with spinal cord injuries.
Previous studies have shown that acidic fibroblast growth factor (aFGF), with peripheral nerve graft, to be beneficial in the repair of complete thoracic spinal cord transaction in rodents, and preliminary reports on the clinical use of aFGF, with or without peripheral nerve graft, have also been favourable. Due the practicalities of using aFGF in actual clinical practice, aFGF was adapted so that it could be used without the need for peripheral nerve grafting. This latest study, which used the modified version of aFGF, aimed to review its effectiveness and safety in humans with spinal cord injuries.
The investigators Wu et al reviewed patients with chronic rather than acute spinal cord injury as patients with chronic injuries have minimal chances of improvement (and therefore, any observed improvements in the study are less likely to be caused by natural recovery). Patients were grouped by the level of spine injury, with half being classified as cervical (C–4 was the most common level of injury) and the other half being classified as thoracolumbar (L–1 was the most common level of injury). As it was an open-label design, all patients received the first 2ml combined dose aFGF and fibrin glue intraoperatively after undergoing a total laminectomy of the injured spinal segments with neurolysis of the injured rootlets (if present) from the adherent granulation tissue. Patients also received “booster” doses at three and six months post surgery. They were then evaluated at three, six, 12, 18, and 24 months intervals; of the original 60, 49 patients completed the 24-month study (26 in the cervical group and 23 in the thoracolumbar group).
In both cervical and thoracolumbar groups, American Spin Injury Association (ASIA) motor scores significantly improved from preoperative levels to 12 and 14 months levels. ASIA scores were also significantly improved at 12 and 24 months in both groups. At 12 months, only 16.67% of patients in the cervical group and 16.67% of the thoracolumbar group saw an improvement in their ASIA impairment scales compared with preoperative levels. However, at 24 months, a significant proportion of both groups (each 30%) had an improvement in these scores. After 24 months, in both groups, neurological levels and functional independence also improved. No adverse events directly related to the aFGF were found.
Wu et al reported: “The current study provides important information on the safety, feasibility, and potential effectiveness of this regimen…As little as one motor level or couple of sensory level improvements may increase the quality of life for these patients.” They add that their study has “elicited more questions than answers”, as information is now needed on the best timing of intervention after injury, the optimum dose, the effective route of administration, and long-term side effects of the treatment. “Prospective, randomised, controlled trials are warranted to corroborate this relatively safe repair strategy.”
Writing in an editorial in the Journal of Neurosurgery Spine, Michael Fehlings (Krembil Neuroscience Centre Spinal Program, Toronto Western Hospital, Canada) and Jefferson Wilson (Department of Surgery, Division of Neurosurgery, University of Canada, Canada) say that it is “entirely” possible that the neurological recovery observed was due to the patients’ natural recovery that was “bolstered” by rehabilitation protocol that all patients received after treatment. They add that they “strongly encourage” Wu et al to undertake a prospective, randomised, controlled study. “Without such evidence, the effectiveness of aFGF for spinal cord injury remains unproven.”
Responding to the editorial, Wu et al said that using a control group in the study would have provided more information on aFGF but added that this would have made sham operations “unavoidable.” “Sham operations were not only opposed by the review committee but also argued by Dr Henrich Cheng [one of the investigators] to be unfair or insensible if we were to enrol participants as a control group. From the perspective of spinal cord injury patients or their families, who would be happy to be enrolled in the control group receiving a sham operation?”
According to Wu et al, randomised trials are less justifiable and more difficult to implement if the safety of an intervention (such as aFGF) has been established. Importantly, before any action to intervene in spinal cord injury is undertaken, Wu et al argue, extreme caution is warranted “because patients are often desperate and vulnerable to false expectations. Psychological support and the sustaining group are crucial because of the inevitable disappointment to the patients regarding the best available treatment according to current medical science.”