The Royal Melbourne Hospital, Grattan St. Parkville, Melbourne, Australia; Centre for Neuroscience, University of Melbourne, Australia.
Pharmacol Ther. 2010 Apr;126(1):82-93. doi: 10.1016/j.pharmthera.2010.01.006. Epub 2010 Feb 1.
Multiple sclerosis (MS) is the commonest cause of progressive neurological disability amongst young, Caucasian adults. MS is considered to be an auto-immune disease that results from an attack against myelin, the layer which surrounds axons. The pathophysiology of MS is complex, with both demyelination and axonal degeneration contributing to what is essentially an inflammatory neurodegenerative disease. Axonal loss is increasingly being accepted as the histopathological correlate of neurological disability. Currently, the underpinnings of neurodegeneration in MS, and how to promote neuroprotection are only partly understood. No established treatments that directly reduce nervous system damage or enhance its repair are currently available. Moreover, the ability of currently available immunomodulatory therapies used to treat MS, such as interferon-beta, to prevent long-term disability is uncertain. Results from short-term randomized-controlled trials suggest a partial benefit with regards to disability outcomes, but this is yet to be established in long-term studies. Novel neuroprotective agents have been identified in preclinical studies but their development is being hampered by the absence of appropriate clinical platforms to test them. In this article, we will discuss some of the principal therapeutic candidates that could provide neuroprotection in MS and emerging methodologies by which to test them.
多发性硬化症（MS）是年轻白种成年人中最常见的进行性神经功能障碍的原因。MS 被认为是一种自身免疫性疾病，是由于针对髓鞘的攻击引起的，髓鞘是包裹轴突的一层。MS 的病理生理学很复杂，脱髓鞘和轴突变性都导致了一种炎症性神经退行性疾病。轴突丢失越来越被认为是神经功能障碍的组织病理学相关性。目前，MS 中神经退行性变的基础以及如何促进神经保护仅部分被理解。目前没有可直接减少神经系统损伤或增强其修复的既定治疗方法。此外，目前用于治疗 MS 的免疫调节疗法（如干扰素-β）是否能预防长期残疾尚不确定。短期随机对照试验的结果表明在残疾结局方面有部分益处，但这仍需在长期研究中确定。已经在临床前研究中确定了一些新的神经保护剂，但由于缺乏适当的临床平台来测试它们，它们的开发受到了阻碍。在本文中，我们将讨论一些可能为 MS 提供神经保护的主要治疗候选药物，以及新兴的测试方法。
