Bose Gauruv, Thebault Simon D X, Fadda Giulia, Brooks John A, Freedman Mark S
Department of Medicine, The University of Ottawa and Ottawa Hospital Research Institute, Canada.
Department of Medicine, The University of Ottawa and Ottawa Hospital Research Institute, Canada; Department of Neurology and Neurosurgery, Montreal Neurological Institute and McGill University Health Centre, Canada.
Neurotherapeutics. 2025 Jul;22(4):e00588. doi: 10.1016/j.neurot.2025.e00588. Epub 2025 Apr 19.
Multiple sclerosis (MS) is a complex, chronic immune-mediated disease characterized by acute and progressive inflammatory damage of the central nervous system. MS manifests clinically with unpredictable neurological symptoms from focal inflammatory attacks as well as gradual neurodegeneration which contribute significantly to long-term disability progression. As treatment options advance, developing more personalized strategies capture heterogeneous mechanisms of injury which may be targeted or predict outcomes has been a focus of ongoing investigation. The role of soluble biomarkers has emerged as a pivotal tool to assist in these goals. Early promising candidates include neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP); these intermediate filaments that are expressed in neurons and astrocytes, respectively, are reliably measurable from blood samples and can reveal clinical and subclinical changes, as well as predict progression. Changes in these biomarkers can indicate a response to therapy, thus potentially be used as endpoints in clinical trials. Furthermore, recent research has identified a potential role of these and other soluble biomarkers in other neuroimmunological conditions including neuromyelitis spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein associated disease (MOGAD), autoimmune encephalitis, neurosarcoidosis, neuropsychiatric involvement in connective tissue disorders and vasculitides, and a host of neurodegenerative conditions. By integrating biomarker analysis into routine clinical assessments, healthcare providers may move toward a more nuanced and individualized care model, better equipped to meet the challenges posed by these multifaceted diseases. Understanding the dynamics of these biomarkers has many applications that can improve personalized medicine in MS.
多发性硬化症(MS)是一种复杂的慢性免疫介导疾病,其特征是中枢神经系统发生急性和进行性炎症损伤。MS在临床上表现为局灶性炎症发作引起的不可预测的神经症状以及逐渐的神经退行性变,这些对长期残疾进展有显著影响。随着治疗选择的进展,制定更个性化的策略以捕捉可能成为治疗靶点或预测结果的异质性损伤机制一直是正在进行的研究重点。可溶性生物标志物的作用已成为实现这些目标的关键工具。早期有前景的候选标志物包括神经丝轻链(NfL)和胶质纤维酸性蛋白(GFAP);这些分别在神经元和星形胶质细胞中表达的中间丝,可以从血液样本中可靠地测量出来,并能揭示临床和亚临床变化以及预测疾病进展。这些生物标志物的变化可以表明对治疗的反应,因此有可能用作临床试验的终点。此外,最近的研究已经确定了这些以及其他可溶性生物标志物在其他神经免疫性疾病中的潜在作用,包括视神经脊髓炎谱系障碍(NMOSD)和髓鞘少突胶质细胞糖蛋白相关疾病(MOGAD)、自身免疫性脑炎、神经结节病、结缔组织疾病和血管炎中的神经精神受累,以及一系列神经退行性疾病。通过将生物标志物分析纳入常规临床评估,医疗保健提供者可能会朝着更细致入微和个性化的护理模式发展,更有能力应对这些多方面疾病带来的挑战。了解这些生物标志物的动态变化有许多应用,可以改善MS的个性化医疗。