Sframeli Maria, Polito Francesca, Vita Gianluca, Macaione Vincenzo, Gitto Eloisa, Vita Giuseppe, Aguennouz M'hammed, Messina Sonia
Department of Clinical and Experimental Medicine, Unit of Neurodegenerative Diseases, University Hospital "G. Martino", Messina, Italy.
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
Acta Neurol Belg. 2025 May 3. doi: 10.1007/s13760-025-02784-1.
The advent of new therapies, such as the antisense oligonucleotide nusinersen, has significantly improved the natural course of spinal muscular atrophy (SMA). Tau proteins and neurofilaments are well known markers of neuro-axonal damages. The neurofilament light protein (NfL) has been proposed as a possible biomarker in SMA. This study aimed to investigate the role of total-tau (t-tau), phosphorylated tau at 181 sites (p-tau 181), NfL, and phosphorylated neurofilament heavy chain (pNfH) proteins as potential cerebrospinal fluid (CSF) biomarkers of disease severity and/or nusinersen treatment response in 14 SMA type 1 patients with a wide age range (2-156 months).
Motor functions were assessed using the "Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders" (CHOP-INTEND) scale at baseline, six months and ten months after treatment. Eight out of 14 patients showed motor improvement. At baseline CSF t-tau and p-tau181 concentration showed a significant negative correlation with age (p = 0.0002 and p = 0.0054 respectively) and a positive correlation with the CHOP-INTEND score (p = 0.0075 and p = 0.0342, respectively). After treatment the tau biomarkers did not show any change, whereas NfL and pNfH concentration significantly decreased (p = 0.0001). The NfL concentration decline correlated to age at baseline (p < 0.05) and to the improvement of the CHOP-INTEND motor score, in the subgroup of patients with a functional improvement above 3 points (p < 0.05).
CSF neurofilaments and particularly NfL may bepromising biomarkers for monitoring treatment response to nusinersen, both in younger and older patients with severe SMA.
新疗法的出现，如反义寡核苷酸诺西那生，显著改善了脊髓性肌萎缩症（SMA）的自然病程。 Tau蛋白和神经丝是神经轴突损伤的知名标志物。神经丝轻链蛋白（NfL）已被提议作为SMA的一种可能的生物标志物。本研究旨在调查总tau（t-tau）、181位点磷酸化tau（p-tau 181）、NfL和磷酸化神经丝重链（pNfH）蛋白作为14例年龄范围广泛（2 - 156个月）的1型SMA患者疾病严重程度和/或诺西那生治疗反应的潜在脑脊液（CSF）生物标志物的作用。
在基线、治疗后6个月和10个月，使用“费城儿童医院婴儿神经肌肉疾病测试”（CHOP-INTEND）量表评估运动功能。14例患者中有8例显示运动功能改善。在基线时，脑脊液t-tau和p-tau181浓度与年龄呈显著负相关（分别为p = 0.0002和p = 0.0054），与CHOP-INTEND评分呈正相关（分别为p = 0.0075和p = 0.0342）。治疗后，tau生物标志物没有显示任何变化，而NfL和pNfH浓度显著下降（p = 0.0001）。NfL浓度下降与基线年龄相关（p < 0.05），并且在功能改善超过3分的患者亚组中与CHOP-INTEND运动评分的改善相关（p < 0.05）。
脑脊液神经丝，特别是NfL，可能是监测诺西那生治疗反应的有前景的生物标志物，无论是在患有严重SMA的年轻患者还是老年患者中。
