Abstract：
OBJECTIVE: Recent studies have suggested that neuroinflammation may play a role in the progression of spinal muscular atrophy (SMA), and this may influence the efficacy of antisense oligonucleotide treatment. This study explored the biomarkers associated with SMA and the efficacy of nusinersen therapy.
METHODS: Fifteen patients with SMA were enrolled and their motor function (World Health Organization motor milestone, Hammersmith Functional Motor Scale Expanded (HFMSE), and Revised Upper Limb Module [RULM] scores, and 6-minute walking test) was evaluated before, during (63 days), and after (6 months) nusinersen treatment. The concentrations of monocyte chemoactive protein 1 (MCP1), tumour necrosis factor-alpha (TNF-α), and interleukin (IL)-10 in the cerebrospinal fluid were measured at the indicated time points, and their correlations with motor function were analysed.
RESULTS: A significant increase in MCP1 was observed after 6 month\'s treatment compared with that before treatment, while TNF-α gradually decreased over the course of treatment. IL-10 levels were negatively correlated with HFMSE scores before treatment, and reductions in IL-10 levels were correlated with improvements in RULM scores.
CONCLUSIONS: This study suggests that neuroinflammation may be associated with the severity of SMA and with the therapeutic effects of nusinersen, which could have clinical implications in the treatment of SMA.
METHODS: Fifteen patients with SMA were enrolled and their motor function (World Health Organization motor milestone, Hammersmith Functional Motor Scale Expanded (HFMSE), and Revised Upper Limb Module [RULM] scores, and 6-minute walking test) was evaluated before, during (63 days), and after (6 months) nusinersen treatment. The concentrations of monocyte chemoactive protein 1 (MCP1), tumour necrosis factor-alpha (TNF-α), and interleukin (IL)-10 in the cerebrospinal fluid were measured at the indicated time points, and their correlations with motor function were analysed.
RESULTS: A significant increase in MCP1 was observed after 6 month\'s treatment compared with that before treatment, while TNF-α gradually decreased over the course of treatment. IL-10 levels were negatively correlated with HFMSE scores before treatment, and reductions in IL-10 levels were correlated with improvements in RULM scores.
CONCLUSIONS: This study suggests that neuroinflammation may be associated with the severity of SMA and with the therapeutic effects of nusinersen, which could have clinical implications in the treatment of SMA.
摘要：
目的：最近的研究表明，神经炎症可能在脊髓性肌萎缩（SMA）的进展中起作用，这可能会影响反义寡核苷酸治疗的功效。本研究探讨了与SMA相关的生物标志物和nusinersen治疗的疗效。
方法：招募了15例SMA患者，他们的运动功能（世界卫生组织运动里程碑，Hammersmith功能电机秤扩展（HFMSE），和修订的上肢模块[RULM]分数，和6分钟步行测试)之前进行了评估，期间（63天），和（6个月）nusinersen治疗后。单核细胞化学活性蛋白1（MCP1）的浓度，肿瘤坏死因子-α（TNF-α），在指定的时间点测量脑脊液中的白细胞介素（IL）-10，并分析了它们与运动功能的相关性。
结果：与治疗前相比，治疗6个月后观察到MCP1显著增加，而TNF-α在治疗过程中逐渐下降。IL-10水平与治疗前HFMSE评分呈负相关,IL-10水平的降低与RULM评分的改善相关.
结论：这项研究表明，神经炎症可能与SMA的严重程度以及nusinersen的治疗效果有关，这可能对SMA的治疗有临床意义。
方法：招募了15例SMA患者，他们的运动功能（世界卫生组织运动里程碑，Hammersmith功能电机秤扩展（HFMSE），和修订的上肢模块[RULM]分数，和6分钟步行测试)之前进行了评估，期间（63天），和（6个月）nusinersen治疗后。单核细胞化学活性蛋白1（MCP1）的浓度，肿瘤坏死因子-α（TNF-α），在指定的时间点测量脑脊液中的白细胞介素（IL）-10，并分析了它们与运动功能的相关性。
结果：与治疗前相比，治疗6个月后观察到MCP1显著增加，而TNF-α在治疗过程中逐渐下降。IL-10水平与治疗前HFMSE评分呈负相关,IL-10水平的降低与RULM评分的改善相关.
结论：这项研究表明，神经炎症可能与SMA的严重程度以及nusinersen的治疗效果有关，这可能对SMA的治疗有临床意义。
