Xing Xiaodong, Zhao Shuyan, Jiang Ruoyu, Jiang Wengao
College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China.
Department of Clinical Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China.
Eur J Pediatr. 2025 May 24;184(6):358. doi: 10.1007/s00431-025-06184-8.
Salbutamol, an agonist of the β2-adrenergic receptor, has demonstrated positive outcomes in spinal muscular atrophy (SMA). This systematic review and meta-analysis aimed to investigate its efficacy and safety in patients with SMA. Four biomedical databases (PubMed, Embase, Web of Science, Cochrane Library) and three conference abstract repositories were systematically searched on 1 February 2025 for related clinical studies. Primary outcomes were the motor function, respiratory function, and the peripheral survival motor neuron (SMN) transcript levels of SMA patients pre- and post-salbutamol. Secondary outcomes included musculoskeletal function metrics, patient-reported symptoms, and adverse events. A total of eight studies involving 154 subjects were included in the final analysis. Qualitative analysis revealed that a significant number of patients reported subjective improvements. Additionally, salbutamol has been shown to improve respiratory function and contribute to weight gain in certain younger individuals. Meta-analysis demonstrated that, in two selected studies, patients under 6 years old showed a substantial improvement in the Revised Upper Limb Module (RULM) scores (mean difference (MD) = 3.89, 95% confidence interval (CI) 0.35-7.43, P = 0.03) with no significant heterogeneity. Salbutamol also elevated the levels of peripheral SMN2 full-length transcripts, with statistical significance observed at 6 months (MD = 25.13, 95% CI 16.12-34.13, P < 0.00001) and sustained through to 12 months.
Salbutamol represents a safe therapeutic option that holds considerable promise in the management of SMA, particularly among clinical responders and younger subgroups. Double-blind, randomized, controlled trials are required to confirm these findings.
• Clinical trials in neuromuscular junction disorders report motor function gains associated with β2-agonists therapy, attributed to both muscle trophic effects and NMJ synaptic modulation. • Salbutamol, a β2-adrenergic receptor agonist, has been shown to increase full-length SMN2 mRNA and functional SMN protein levels in SMA patient-derived fibroblasts.
• Salbutamol possesses the potential to improve motor function in patients with SMA and represents a safe therapeutic option that holds considerable promise in the management of SMA. • The potential mechanism of salbutamol in treating SMA patients may involve enhancing SMN2 transcript expression via cAMP regulation and increasing SMN protein levels by inhibiting ubiquitin-mediated SMN degradation through the β2 adrenergic receptor-PKA pathway. • Salbutamol emerges as a cost-effective and viable option for SMA patients in underdeveloped regions who lack access to or cannot afford disease-modifying treatments.
沙丁胺醇是β2肾上腺素能受体激动剂，已在脊髓性肌萎缩症（SMA）中显示出积极效果。本系统评价和荟萃分析旨在研究其在SMA患者中的疗效和安全性。于2025年2月1日对四个生物医学数据库（PubMed、Embase、Web of Science、Cochrane图书馆）和三个会议摘要库进行了系统检索，以查找相关临床研究。主要结局为SMA患者在使用沙丁胺醇前后的运动功能、呼吸功能以及外周存活运动神经元（SMN）转录水平。次要结局包括肌肉骨骼功能指标、患者报告的症状和不良事件。最终分析纳入了八项研究，共154名受试者。定性分析显示，大量患者报告有主观改善。此外，沙丁胺醇已被证明可改善呼吸功能，并有助于某些较年轻个体的体重增加。荟萃分析表明，在两项选定研究中，6岁以下患者的改良上肢模块（RULM）评分有显著改善（平均差值（MD）=3.89，95%置信区间（CI）0.35 - 7.43，P = 0.03），且无显著异质性。沙丁胺醇还提高了外周SMN2全长转录本水平，在6个月时具有统计学意义（MD = 25.13，95%CI 16.12 - 34.13，P < 0.00001），并持续至12个月。
沙丁胺醇是一种安全的治疗选择，在SMA的治疗中具有很大前景，尤其是在临床反应者和较年轻亚组中。需要进行双盲、随机、对照试验来证实这些发现。
• 神经肌肉接头疾病的临床试验报告了与β2激动剂治疗相关的运动功能改善，这归因于肌肉营养作用和神经肌肉接头突触调节。• 沙丁胺醇作为一种β2肾上腺素能受体激动剂，已被证明可增加SMA患者来源的成纤维细胞中全长SMN2 mRNA和功能性SMN蛋白水平。
• 沙丁胺醇具有改善SMA患者运动功能的潜力，是一种安全的治疗选择，在SMA的治疗中具有很大前景。• 沙丁胺醇治疗SMA患者的潜在机制可能包括通过cAMP调节增强SMN2转录表达，以及通过β2肾上腺素能受体 - PKA途径抑制泛素介导的SMN降解来增加SMN蛋白水平。• 对于缺乏或负担不起疾病修饰治疗的欠发达地区的SMA患者，沙丁胺醇是一种经济有效且可行的选择。
