Adult Neurology Department, Citadelle Hospital, 1 Boulevard Du 12e De Ligne, 4000 Liege, Belgium.
MDUK Oxford Neuromuscular Center, Department of Paediatrics, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 9DU, UK.
Int J Mol Sci. 2024 Aug 12;25(16):8763. doi: 10.3390/ijms25168763.
Clinical trials with treatments inhibiting myostatin pathways to increase muscle mass are currently ongoing in spinal muscular atrophy. Given evidence of potential myostatin pathway downregulation in Spinal Muscular Atrophy (SMA), restoring sufficient myostatin levels using disease-modifying treatments (DMTs) might arguably be necessary prior to considering myostatin inhibitors as an add-on treatment. This retrospective study assessed pre-treatment myostatin and follistatin levels' correlation with disease severity and explored their alteration by disease-modifying treatment in SMA. We retrospectively collected clinical characteristics, motor scores, and mysotatin and follistatin levels between 2018 and 2020 in 25 Belgian patients with SMA (SMA1 ( = 13), SMA2 ( = 6), SMA 3 ( = 6)) and treated by nusinersen. Data were collected prior to treatment and after 2, 6, 10, 18, and 30 months of treatment. Myostatin levels correlated with patients' age, weight, SMA type, and motor function before treatment initiation. After treatment, we observed correlations between myostatin levels and some motor function scores (i.e., MFM32, HFMSE, 6MWT), but no major effect of nusinersen on myostatin or follistatin levels over time. In conclusion, further research is needed to determine if DMTs can impact myostatin and follistatin levels in SMA, and how this could potentially influence patient selection for ongoing myostatin inhibitor trials.
目前，在脊髓性肌萎缩症中正在进行抑制肌肉生长抑制素途径以增加肌肉量的临床试验。鉴于肌肉生长抑制素途径在脊髓性肌萎缩症中可能存在潜在下调的证据，在考虑将肌肉生长抑制素抑制剂作为附加治疗方法之前，使用疾病修饰治疗（DMT）恢复足够的肌肉生长抑制素水平可能是必要的。这项回顾性研究评估了治疗前肌肉生长抑制素和卵泡抑素水平与疾病严重程度的相关性，并探讨了它们在脊髓性肌萎缩症中通过疾病修饰治疗的变化。我们回顾性地收集了 2018 年至 2020 年间在 25 名接受 nusinersen 治疗的比利时脊髓性肌萎缩症患者（SMA1（n = 13）、SMA2（n = 6）、SMA3（n = 6））的临床特征、运动评分以及肌肉生长抑制素和卵泡抑素水平的数据。数据在治疗前以及治疗后 2、6、10、18 和 30 个月收集。肌肉生长抑制素水平与患者治疗前的年龄、体重、SMA 类型和运动功能相关。治疗后，我们观察到肌肉生长抑制素水平与一些运动功能评分（即 MFM32、HFMSE、6MWT）之间存在相关性，但 nusinersen 对肌肉生长抑制素或卵泡抑素水平在时间上没有显著影响。总之，需要进一步的研究来确定 DMT 是否可以影响 SMA 中的肌肉生长抑制素和卵泡抑素水平，以及这如何可能影响正在进行的肌肉生长抑制素抑制剂试验中患者的选择。
