Department of Neurology, University Hospital Carl Gustav Carus at TU Dresden, Fetscherstraße 74, 01307, Dresden, Germany.
Department of Neurology and Center for Translational Neuro- and Behavioral Science (C-TNBS), University Medicine Essen, Essen, Germany.
J Neurol. 2023 Sep;270(9):4157-4178. doi: 10.1007/s00415-023-11787-y. Epub 2023 Jun 8.
5q-associated spinal muscular atrophy (SMA) is a rare genetic disease caused by mutations in the SMN1 gene, resulting in a loss of functional SMN protein and consecutive degeneration of motor neurons in the ventral horn. The disease is clinically characterized by proximal paralysis and secondary skeletal muscle atrophy. New disease-modifying drugs driving SMN gene expression have been developed in the past decade and have revolutionized SMA treatment. The rise of treatment options led to a concomitant need of biomarkers for therapeutic guidance and an improved disease monitoring. Intensive efforts have been undertaken to develop suitable markers, and numerous candidate biomarkers for diagnostic, prognostic, and predictive values have been identified. The most promising markers include appliance-based measures such as electrophysiological and imaging-based indices as well as molecular markers including SMN-related proteins and markers of neurodegeneration and skeletal muscle integrity. However, none of the proposed biomarkers have been validated for the clinical routine yet. In this narrative review, we discuss the most promising candidate biomarkers for SMA and expand the discussion by addressing the largely unfolded potential of muscle integrity markers, especially in the context of upcoming muscle-targeting therapies. While the discussed candidate biomarkers hold potential as either diagnostic (e.g., SMN-related biomarkers), prognostic (e.g., markers of neurodegeneration, imaging-based markers), predictive (e.g., electrophysiological markers) or response markers (e.g., muscle integrity markers), no single measure seems to be suitable to cover all biomarker categories. Hence, a combination of different biomarkers and clinical assessments appears to be the most expedient solution at the time.
5q 相关脊髓性肌萎缩症（SMA）是一种罕见的遗传性疾病，由 SMN1 基因突变引起，导致功能性 SMN 蛋白缺失，随后腹角运动神经元退化。该疾病的临床特征为进行性近端肌无力和继发性骨骼肌萎缩。过去十年中，已经开发出了一些新的能够驱动 SMN 基因表达的疾病修饰药物，从而彻底改变了 SMA 的治疗方法。随着治疗选择的增加，同时也需要有治疗指导和疾病监测的生物标志物。因此，人们进行了大量的努力来开发合适的标志物，并已经确定了许多具有诊断、预后和预测价值的候选生物标志物。最有前途的标志物包括基于仪器的测量，如电生理学和影像学指标，以及包括 SMN 相关蛋白和神经退行性变和骨骼肌完整性标志物在内的分子标志物。然而，目前还没有任何一种提出的生物标志物被验证可用于临床常规。在本综述中，我们讨论了 SMA 最有前途的候选生物标志物，并通过讨论肌肉完整性标志物的广泛潜在应用来扩展讨论，特别是在即将出现的肌肉靶向治疗的背景下。虽然所讨论的候选生物标志物具有作为诊断（例如，SMN 相关生物标志物）、预后（例如，神经退行性变标志物、影像学标志物）、预测（例如，电生理学标志物）或反应标志物（例如，肌肉完整性标志物）的潜力，但似乎没有单一的指标可以适用于所有的生物标志物类别。因此，在目前的情况下，不同的生物标志物和临床评估的组合似乎是最便捷的解决方案。
