Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Curr Opin Neurol. 2022 Jun 1;35(3):293-298. doi: 10.1097/WCO.0000000000001044.
Disability progression in multiple sclerosis (MS) is strongly linked to central nervous system (CNS)-specific pathological processes that occur throughout all disease stages, but that become clinically evident in later phases of the disease. We here discuss current views and concepts for targeting progressive MS.
Detailed clinical assessment of MS patients has identified an even closer entanglement of relapse-remitting and progressive disease, leading to novel concepts such as 'progression independent of relapse activity'. Evolving clinical concepts together with a focus on molecular (neurofilament light chain) and imaging (paramagnetic rim lesions) biomarkers might specifically identify patients at risk of developing progressive MS considerably earlier than before. A multitude of novel treatment approaches focus either on direct neuroaxonal protection or myelin regeneration or on beneficially modulating CNS-intrinsic or innate immune inflammation. Although some long-awaited trials have recently been unsuccessful, important lessons could still be drawn from novel trial designs providing frameworks for future clinical studies.
Targeting progressive disease biology and repairing established damage is the current central challenge in the field of MS. Especially, the compartmentalized adaptive and innate CNS inflammation is an attractive target for novel approaches, probably as a combinatory approach together with neuroprotective or myelin regenerating strategies.
多发性硬化症（MS）的残疾进展与中枢神经系统（CNS）特异性病理过程密切相关，这些过程发生在所有疾病阶段，但在疾病的后期阶段才会在临床上显现出来。我们在此讨论针对进展性 MS 的当前观点和概念。
对 MS 患者的详细临床评估发现，复发缓解型和进展型疾病之间的联系更加紧密，导致了一些新的概念，如“与复发活动无关的进展”。不断发展的临床概念以及对分子（神经丝轻链）和影像学（顺磁性边缘病变）生物标志物的关注，可能会比以前更早地识别出有进展性 MS 风险的患者。大量新的治疗方法要么专注于直接的神经轴突保护或髓鞘再生，要么是有益地调节中枢神经系统内在或固有免疫炎症。虽然最近一些期待已久的试验失败了，但仍可以从提供未来临床研究框架的新试验设计中吸取重要的经验教训。
针对进展性疾病生物学和修复已建立的损伤是 MS 领域目前的核心挑战。特别是，中枢神经系统的适应性和固有炎症的分隔是新方法的一个有吸引力的目标，可能作为一种联合治疗方法，与神经保护或髓鞘再生策略相结合。
