Department of Neurology, University of California, San Francisco, San Francisco, CA.
Ann Neurol. 2013 Sep;74(3):317-27. doi: 10.1002/ana.24009.
We have entered a golden era in multiple sclerosis (MS) research. Two decades ago, our understanding of the disease was largely descriptive and there were no approved therapies to modify the natural history of MS. Today, delineation of immune pathways relevant to MS have been clarified; a comprehensive map of genes that influence risk compiled; clues to environmental triggers identified; noninvasive in vivo monitoring of the MS disease process has been revolutionized by high-field MRI; and many effective therapies for the early, relapsing, component of MS now exist. However, major challenges remain. We still have no useful treatment for progressive MS (the holy grail of MS research), no means to repair injured axons or protect neurons, and extremely limited evidence to guide treatment decisions. Recent advances have set in place a foundation for development of increasingly selective immunotherapy for patients; application of genetic and genomic discoveries to improve therapeutic options; development of remyelination or neuroprotection therapies for progressive MS; and integrating clinical, imaging and genomic data for personalized medicine. MS has now advanced from the backwaters of autoimmune disease research to the front-line, and definitive answers, including cures, are now realistic goals for the next decade. Many of the breakthrough discoveries in MS have also resulted from meaningful interactions across disciplines, and especially from translational and basic scientists working closely with clinicians, highlighting that the clinical value of discoveries are most often revealed when ideas developed in the laboratory are tested at the bedside.
我们正处在多发性硬化症(MS)研究的黄金时代。二十年前,我们对该疾病的了解在很大程度上是描述性的,并且没有批准的疗法可以改变 MS 的自然病程。如今,与 MS 相关的免疫途径已经得到阐明;编制了影响风险的综合基因图谱;确定了环境触发因素的线索;高场 MRI 彻底改变了 MS 疾病过程的非侵入性体内监测;现在存在许多针对 MS 早期复发成分的有效疗法。但是,仍存在重大挑战。我们仍然没有针对进展性 MS(MS 研究的圣杯)的有效治疗方法,没有修复受损轴突或保护神经元的方法,并且指导治疗决策的证据非常有限。最近的进展为开发针对患者的越来越具选择性的免疫疗法奠定了基础;将遗传和基因组发现应用于改善治疗选择;为进展性 MS 开发髓鞘再生或神经保护疗法;以及将临床,成像和基因组数据整合用于个性化医学。MS 现在已经从自身免疫疾病研究的边缘领域发展到了前沿领域,在接下来的十年中,包括治愈在内的明确答案现在是现实的目标。MS 中的许多突破性发现也源于跨学科的有意义的互动,尤其是转化和基础科学家与临床医生密切合作,这突显了当实验室中开发的想法在床边得到检验时,发现的临床价值通常才会得到体现。