Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Department of Neurology, Universitätsklinikum Halle (Saale), Halle (Saale), Germany.
Ann Clin Transl Neurol. 2022 Sep;9(9):1437-1448. doi: 10.1002/acn3.51645. Epub 2022 Aug 11.
Activated astroglia is involved in the pathophysiology of neurodegenerative diseases and has also been described in animal models of spinal muscular atrophy (SMA). Given the urgent need of biomarkers for treatment monitoring of new RNA-modifying and gene replacement therapies in SMA, we examined glial fibrillary acidic protein concentrations in cerebrospinal fluid (cGFAP) as a marker of astrogliosis in SMA.
58 adult patients and 21 children with genetically confirmed 5q-associated SMA from four German motor neuron disease specialist care centers and 30 age- and sex-matched controls were prospectively included in this study. cGFAP was measured and correlated to motor performance and disease severity. Additionally, we compared cGFAP with neurofilament light chain concentrations in cerebrospinal fluid (cNfL).
cGFAP concentrations did not differ from controls but showed higher levels in more severely affected patients after adjustment for patients' age. Normalized cNfL values were associated with disease severity. Within 14 months of nusinersen treatment, cGFAP concentrations did not change, while cNfL decreased significantly.
cGFAP is not an outstanding biomarker in SMA, but might support the hypothesis that glial activation is involved in SMA pathology. Unlike previously suggested, cNfL may be a promising biomarker also in adult patients with SMA, which should be subject to further investigations.
激活的星形胶质细胞参与神经退行性疾病的病理生理学，也在脊髓性肌萎缩症（SMA）的动物模型中有所描述。鉴于 SMA 新的 RNA 修饰和基因替换治疗的治疗监测对生物标志物的迫切需求，我们研究了星形胶质细胞增生的标志物——脑脊液中的胶质纤维酸性蛋白（cGFAP）浓度。
本前瞻性研究纳入了来自四个德国运动神经元疾病专家护理中心的 58 名成年患者和 21 名经基因证实的 5q 相关 SMA 儿童患者，以及 30 名年龄和性别匹配的对照者。测量了 cGFAP 浓度，并与运动表现和疾病严重程度相关联。此外，我们比较了 cGFAP 与脑脊液中神经丝轻链浓度（cNfL）。
cGFAP 浓度与对照组无差异，但在调整患者年龄后，在病情较重的患者中水平较高。正常化的 cNfL 值与疾病严重程度相关。在 nusinersen 治疗的 14 个月内，cGFAP 浓度没有变化，而 cNfL 显著下降。
cGFAP 不是 SMA 的突出生物标志物，但可能支持星形胶质细胞激活参与 SMA 病理的假说。与先前的建议不同，cNfL 也可能是 SMA 成年患者有前途的生物标志物，应进一步研究。
