Acidic fibroblast growth factor for repair of human spinal cord injury: a clinical trial

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>The study aimed to verify the safety and feasibility of applying acidic fibroblast growth factor (aFGF) with fibrin glue in combination with surgical neurolysis for nonacute spinal cord injury.</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>This open-label, prospective, uncontrolled human clinical trial recruited 60 patients with spinal cord injuries (30 cervical and 30 thoracolumbar). The mean patient age was 36.5 ± 15.33 (mean ± SD) years, and the male/female ratio was 3:1. The mean time from injury to treatment was 25.7 ± 26.58 months, and the cause of injury included motor vehicle accident (26 patients [43.3%]), fall from a height (17 patients [28.3%]), sports (4 patients [6.7%]), and other (13 patients [21.7%]). Application of aFGF with fibrin glue and duraplasty was performed via laminectomy, and an adjuvant booster of combined aFGF and fibrin glue (2 ml) was given at 3 and 6 months postsurgery via lumbar puncture. Outcome measurements included the American Spinal Injury Association (ASIA) motor scores, sensory scores, impairment scales, and neurological levels. Examination of functional independence measures, visual analog scale, MR imaging, electrophysiological and urodynamic studies, hematology and biochemistry tests, tumor markers, and serum inflammatory cytokines were all conducted. All adverse events were monitored and reported. Exclusions were based on refusal, unrelated adverse events, or failure to participate in the planned rehabilitation.</jats:p></jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Forty-nine patients (26 with cervical and 23 with thoracolumbar injuries) completed the 24-month trial. Compared with preoperative conditions, the 24-month postoperative ASIA motor scores improved significantly in the cervical group (from 27.6 ± 15.55 to 37.0 ± 19.93, p &lt; 0.001) and thoracolumbar group (from 56.8 ± 9.21 to 60.7 ± 10.10, p &lt; 0.001). The ASIA sensory scores also demonstrated significant improvement in light touch and pinprick in both groups: from 55.8 ± 24.89 to 59.8 ± 26.47 (p = 0.049) and 56.3 ± 23.36 to 62.3 ± 24.87 (p = 0.003), respectively, in the cervical group and from 75.7 ± 15.65 to 79.2 ± 15.81 (p &lt; 0.001) and 78.2 ± 14.72 to 82.7 ± 16.60 (p &lt; 0.001), respectively, in the thoracolumbar group. At 24-month follow-up, the ASIA impairment scale improved significantly in both groups (30% cervical [p = 0.011] and 30% thoracolumbar [p = 0.003]). There was also significant improvement in neurological level in the cervical (from 5.17 ± 1.60 to 6.27 ± 3.27, p = 0.022) and thoracolumbar (from 18.03 ± 4.19 to 18.67 ± 3.96, p = 0.001) groups. The average sum of motor items in functional independence measure also had significant improvement in both groups (p &lt; 0.05). The walking/wheelchair locomotion subscale showed increased percentages of patients who were ambulatory (from 3.4% to 13.8% and from 17.9% to 35.7% in the cervical and thoracolumbar groups, respectively). There were no related adverse events.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>The use of aFGF for spinal cord injury was safe and feasible in the present trial. There were significant improvements in ASIA motor and sensory scale scores, ASIA impairment scales, neurological levels, and functional independence measure at 24 months after treatment. Further large-scale, randomized, and controlled investigations are warranted to evaluate the efficacy and long-term results.</jats:p></jats:sec>

Regulation of Caveolin-1 and Junction Proteins by bFGF Contributes to the Integrity of Blood–Spinal Cord Barrier and Functional Recovery

“…In acute stroke, a 24-h intravenous infusion of 5 mg bFGF has been confirmed as safe for patients and results in an improved outcome [52]. As the therapeutic potential of bFGF has been well recognized for decades, and the neuroprotection of FGF in SCI has already been translated to clinical trials [53,54], it is reasonable to believe that bFGF will be applied to the clinic. In addition, the combination of a delivery system or special biomaterials to increase its stability and prolong the half-life might contribute to the utility of bFGF.…”

Risk of spinal cord injury in patients with cervical spondylotic myelopathy and ossification of posterior longitudinal ligament: a national cohort study

“…6,[30][31][32][33] The present study has the merit of using the national cohort in an area of higher prevalence of both SCI and OPLL to demonstrate risk factors of SCI in patients with CSM. The study provides a reference guide for future management of CSM.…”

Neural Stem Cells and Induced Neurons for Nerve Injury Repair

“…Notably, Chen et al developed an FGF1-based SCI repair strategy and designed a clinical trial to test the efficacy and safety of using FGF1 in combination with surgical intervention in human SCI. Through the clinical trial, they demonstrated that using FGF1 is safe and feasible for treating SCI [87]. Significant improvements were observed in American Spinal Injury Association motor and sensory scale scores, ASIA impairment scales, neurological levels, and the functional independence measure 24 mo after treatment [87].…”

“…Through the clinical trial, they demonstrated that using FGF1 is safe and feasible for treating SCI [87]. Significant improvements were observed in American Spinal Injury Association motor and sensory scale scores, ASIA impairment scales, neurological levels, and the functional independence measure 24 mo after treatment [87]. Accumulating evidence suggests that FGF1 can be used to treat SCI and peripheral nerve injury.…”

“…A combination of FGF1, biomaterials, and iNSCs/iNs has promising clinical applications. Notably, peripheral nerve grafts and FGF1 have not only repaired the hind limb of adult paraplegic rats [17,21] but also exerted therapeutic effects on patients with spinal cord injury (SCI) and common peroneal nerve lesions [86,87]. Thus, direct FGF1 treatment may benefit patients.…”