Giorgia Querin, Gomez Garcia de la Banda Marta, Smeriglio Piera
APHP, Service de Neuromyologie, Hôpital Pitié-Salpêtrière, Centre Référent pour les Maladies Neuromusculaires Nord/Est/Ile de France, Paris, France.
Institut de Myologie, I-Motion Clinical Trials Platform, Paris, France.
Front Neurol. 2023 Nov 13;14:1226969. doi: 10.3389/fneur.2023.1226969. eCollection 2023.
Spinal muscular atrophy (SMA) is a lower motor neuron disease due to biallelic mutations in the gene on chromosome 5. It is characterized by progressive muscle weakness of limbs, bulbar and respiratory muscles. The disease is usually classified in four different phenotypes (1-4) according to age at symptoms onset and maximal motor milestones achieved. Recently, three disease modifying treatments have received approval from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), while several other innovative drugs are under study. New therapies have been game changing, improving survival and life quality for SMA patients. However, they have also intensified the need for accurate biomarkers to monitor disease progression and treatment efficacy. While clinical and neurophysiological biomarkers are well established and helpful in describing disease progression, there is a great need to develop more robust and sensitive circulating biomarkers, such as proteins, nucleic acids, and other small molecules. Used alone or in combination with clinical biomarkers, they will play a critical role in enhancing patients' stratification for clinical trials and access to approved treatments, as well as in tracking response to therapy, paving the way to the development of individualized therapeutic approaches. In this comprehensive review, we describe the foremost circulating biomarkers of current significance, analyzing existing literature on non-treated and treated patients with a special focus on neurofilaments and circulating miRNA, aiming to identify and examine their role in the follow-up of patients treated with innovative treatments, including gene therapy.
脊髓性肌萎缩症（SMA）是一种由于5号染色体上该基因双等位基因突变导致的下运动神经元疾病。其特征为肢体、延髓和呼吸肌进行性肌无力。该疾病通常根据症状出现的年龄和达到的最大运动里程碑分为四种不同的表型（1 - 4型）。最近，三种疾病修正疗法已获得美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）的批准，同时还有其他几种创新药物正在研究中。新疗法改变了局面，提高了SMA患者的生存率和生活质量。然而，它们也加剧了对准确生物标志物的需求，以监测疾病进展和治疗效果。虽然临床和神经生理生物标志物已得到充分确立且有助于描述疾病进展，但迫切需要开发更强大、更敏感的循环生物标志物，如蛋白质、核酸和其他小分子。单独使用或与临床生物标志物联合使用，它们将在加强患者临床试验分层和获得批准治疗方面发挥关键作用，以及在跟踪治疗反应方面发挥关键作用，为个性化治疗方法的发展铺平道路。在这篇全面综述中，我们描述了当前具有重要意义的首要循环生物标志物，分析了关于未治疗和已治疗患者的现有文献，特别关注神经丝和循环微小RNA，旨在识别和研究它们在接受创新治疗（包括基因治疗）患者随访中的作用。
