Biochemical and clinical biomarkers in adult SMA 3-4 patients treated with nusinersen for 22 months.
Biochemical and clinical biomarkers in adult SMA 3-4 patients treated with nusinersen for 22 months.
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DOI：
10.1002/acn3.51625
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发表时间：
2022-08
影响因子：
5.3
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中科院分区：
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研究脊髓性肌萎缩症（SMA）成人患者脑脊液（CSF）和血清中疾病进展的生物标志物。此外，我们在比先前报告的6-14个月更长的随访期内评估了SMA成人患者对nusinersen治疗的临床应答。在这项前瞻性研究中，我们纳入了16例接受nusinersen治疗超过22个月的3-4型SMA成人患者。我们评估了基线、第6、14和22个月时作为CSF中神经炎性生物标志物的壳三糖苷酶-1（CHIT-1）和几丁质酶-3样蛋白1（YKL-40），以及作为CSF和血清中神经退行性标志物的神经丝轻链（NfL）和重链（pNfH），以及广泛的临床结局指标。在整个22个月治疗期间，CSF中CHIT 1水平显著升高（p = 0.048），pNfH水平显著降低（p = 0.022），但两者均与临床结局指标无关。YKL-40与CSF中的神经丝密切相关（rho = 0.76），并且在改良上肢模块（RULM）改善的患者中显著降低（p = 0.037）。最后，治疗22个月后，患者的握力、手部运动功能、医学研究理事会（MRC）总分和呼气峰流速（PEF）均有显著改善。CSF中的YKL-40与nusinersen治疗期间的临床改善相关。相反，CSF中CHIT 1和pNfH在治疗期间显著变化，但与临床结局无关。最后，我们证明了nusinersen治疗成人22个月后的持续临床效果。
To investigate biomarkers of disease progression in cerebrospinal fluid (CSF) and serum in adult patients with spinal muscular atrophy (SMA). Furthermore, we assess the clinical response to nusinersen treatment in adults with SMA over a longer follow‐up period than the previously reported 6–14 months. We included 16 adults with SMA type 3–4 for nusinersen treatment over 22 months in this prospective study. We evaluated chitotriosidase‐1 (CHIT1) and chitinase‐3‐like protein 1 (YKL‐40) as neuroinflammatory biomarkers in CSF, and neurofilament light chain (NfL) and heavy chain (pNfH) as neurodegenerative markers in CSF and serum at baseline, month 6, 14 and 22, together with a wide range of clinical outcome measures. Levels of CHIT1 increased significantly (p = 0.048) throughout the 22‐month treatment period and pNfH decreased significantly (p = 0.022) in CSF, but both did not correlate with clinical outcome measures. YKL‐40 correlated strongly with neurofilaments in CSF (rho = 0.76) and decreased significantly (p = 0.037) in patients with improvements in the revised upper limb module (RULM). Finally, patients showed significant improvements in hand grip strength, hand motor function, medical research council (MRC) sum score, and peak expiratory flow (PEF) after 22 months of treatment. YKL‐40 in CSF correlated with clinical improvements during nusinersen treatment. In contrast, CHIT1 and pNfH in CSF changed significantly during treatment but did not correlate with clinical outcomes. Finally, we demonstrated a sustained clinical effect of nusinersen treatment in adults after 22 months.