Cunningham Catriona J, Viskontas Mindaugas, Janowicz Krzysztof, Sani Yasmin, Håkansson Malin E, Heidari Anastasia, Huang Wenlong, Bo Xuenong
Institute of Medical Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Aberdeen, UK.
Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Neural Regen Res. 2023 Feb;18(2):299-305. doi: 10.4103/1673-5374.347941.
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, Tau = 2.13, I = 83.6%) and axonal regrowth (SMD: 2.78, 95% CI: 1.92-3.65, Tau = 4.13, I = 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.
目前，创伤性脊髓损伤尚无治愈方法，但一种显示出前景的治疗方法是基因疗法。在这项系统评价和荟萃分析中，我们旨在评估基因疗法在脊髓损伤临床前模型中的疗效以及偏倚风险。在这项在国际前瞻性系统评价注册库（注册号：CRD42020185008）注册的荟萃分析中，我们通过检索PubMed、科学网和Embase数据库，确定了以英文发表的相关体内对照研究。未对发表年份进行限制，最后一次文献检索于2020年8月3日进行。然后，我们使用限制最大似然估计器进行随机效应荟萃分析。共有71项研究符合我们的纳入标准，并被纳入系统评价。我们的结果表明，总体而言，基因疗法与运动评分改善相关（标准化均数差[SMD]：2.07，95%置信区间[CI]：1.68 - 2.47，Tau = 2.13，I² = 83.6%）和轴突再生（SMD：2.78，95%CI：1.92 - 3.65，Tau = 4.13，I² = 85.5%）。两个结局指标的漏斗图均存在显著不对称，表明存在发表偏倚。我们使用改良的CAMARADES（实验研究中动物数据的荟萃分析和综述协作方法）清单来评估偏倚风险，发现中位数评分为4（四分位间距：3 - 5）。特别是，缺乏分配隐藏和样本量计算的报告。总之，基因疗法作为脊髓损伤修复的治疗方法显示出前景，但对于应靶向哪些基因尚无共识。
