Abstract: Currently, there is no cure for traumatic spinal cord injury but one therapeutic approach showing promise is gene therapy. In this systematic review and meta-analysis, we aim to assess the efficacy of gene therapies in pre-clinical models of spinal cord injury and the risk of bias. In this meta-analysis, registered at PROSPERO (Registration ID: CRD42020185008), we identified relevant controlled in vivo studies published in English by searching the PubMed, Web of Science, and Embase databases. No restrictions of the year of publication were applied and the last literature search was conducted on August 3, 2020. We then conducted a random-effects meta-analysis using the restricted maximum likelihood estimator. A total of 71 studies met our inclusion criteria and were included in the systematic review. Our results showed that overall, gene therapies were associated with improvements in locomotor score (standardized mean difference [SMD]: 2.07, 95% confidence interval [CI]: 1.68–2.47, Tau2 = 2.13, I2 = 83.6%) and axonal regrowth (SMD: 2.78, 95% CI: 1.92–3.65, Tau2 = 4.13, I2 = 85.5%). There was significant asymmetry in the funnel plots of both outcome measures indicating the presence of publication bias. We used a modified CAMARADES (Collaborative Approach to Meta-Analysis and Review of Animal Data in Experimental Studies) checklist to assess the risk of bias, finding that the median score was 4 (IQR: 3–5). In particular, reports of allocation concealment and sample size calculations were lacking. In conclusion, gene therapies are showing promise as therapies for spinal cord injury repair, but there is no consensus on which gene or genes should be targeted.

Key words: animal models, gene delivery, meta-analysis, regenerative medicine, spinal cord injury, systematic review, viral vectors