Seo Gigyo, Kim Saeyoon, Byun Jun Chul, Kwon Soonhak, Lee Yun Jeong
Department of Pediatrics, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea.
Department of Pediatrics, School of Medicine, Yeungnam University, Daegu, South Korea.
Brain Dev. 2023 Nov;45(10):554-563. doi: 10.1016/j.braindev.2023.07.005. Epub 2023 Aug 3.
This study aimed to evaluate the neurofilament light chain (NfL) as a biomarker for treatment responses in children with a broad spectrum of spinal muscular atrophy (SMA) under nusinersen treatment.
We measured NfL levels in serum (sNfL) and cerebrospinal fluid (cNfL) in nusinersen-treated patients with SMA and children without neurologic disorders. Correlations between cNfL and sNfL levels and motor function scores were analyzed.
sNfL and cNfL levels were measured in eight patients with SMA (SMA type 1, n = 3; SMA type 2, n = 5). sNfL levels were strongly correlated with cNfL levels regardless of the SMA subtype (r = 0.97, P < 0.001). Patients with SMA type 1 had higher baseline cNfL and sNfL levels before treatment initiation than those with SMA type 2 and neurologically healthy children. In patients with acute stage of SMA type 1 and 2, the NfL level rapidly decreased during the nusinersen treatment loading phase followed by stabilization at a lower plateau level. In contrast, in a patient with a chronic stage of SMA type 2, the NfL level remained within the normal range with no apparent downward trend. Motor function scores showed a tendency toward an inverse correlation with NfL levels in patients with acute stage although not in patients with chronic stage.
cNfL and sNfL levels can be promising biomarkers for monitoring treatment response in patients within their acute stage, particularly in SMA type 1, although not in patients with a chronic stage of SMA type 2.
本研究旨在评估神经丝轻链（NfL）作为一种生物标志物，用于监测接受诺西那生治疗的广泛类型脊髓性肌萎缩症（SMA）患儿的治疗反应。
我们测量了接受诺西那生治疗的SMA患者以及无神经系统疾病儿童的血清（sNfL）和脑脊液（cNfL）中的NfL水平。分析了cNfL和sNfL水平与运动功能评分之间的相关性。
对8例SMA患者（1型SMA，n = 3；2型SMA，n = 5）进行了sNfL和cNfL水平测量。无论SMA亚型如何，sNfL水平与cNfL水平均呈强相关（r = 0.97，P < 0.001）。1型SMA患者在开始治疗前的基线cNfL和sNfL水平高于2型SMA患者和神经功能正常的儿童。在1型和2型SMA急性期患者中，诺西那生治疗负荷期NfL水平迅速下降，随后稳定在较低的平台水平。相比之下，1例2型SMA慢性期患者的NfL水平保持在正常范围内，无明显下降趋势。急性期患者的运动功能评分与NfL水平呈负相关趋势，而慢性期患者则不然。
cNfL和sNfL水平有望作为监测急性期患者，特别是1型SMA患者治疗反应的生物标志物，而不适用于2型SMA慢性期患者。
