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首页> 外文期刊>Journal of neurology >Alternatives to current disease-modifying treatment in MS: what do we need and what can we expect in the future?
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Alternatives to current disease-modifying treatment in MS: what do we need and what can we expect in the future?

机译：MS中目前可改善疾病的治疗方法的替代方案：我们需要什么，将来又能期待什么？

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Disease-modifying treatments (DMTs) for multiple sclerosis (MS) are now widely available, and their beneficial effects on relapse rates, magnetic resonance imaging outcomes and, in some cases, relapse-related disability have been shown in numerous clinical studies. However, as these treatments are only partially effective in halting the MS disease process, the search for improved treatment regimens and novel therapies must continue. Strategies to improve our therapeutic armamentarium have to take into account the different phases or parts of the pathogenesis of the disease. Available treatments address systemic immune dysfunction, blood-brain barrier permeability and the inflammatory process in the central nervous system. Currently, patients who fail to respond adequately to first-line DMTs are often considered as candidates for intensive immunosuppression with cytostatic agents or even autologous stem cell transplantation.However, new approaches are being developed. Combination therapies offer an alternative approach that may have considerable potential to improve therapeutic yield and, although likely to present considerable challenges in terms of trial design, this certainly seems to be a logical step forward in view of the complex pathology of MS. Several new drugs are also being developed with the aim of providing more effective, convenient and/or specific modulation of the inflammatory component of the disease. These treatments include humanised monoclonal antibodies such as the anti-VLA-4 antibody natalizumab, inhibitors of intracellular activation, signalling pathways and T-cell proliferation, and oral immunomodulators such as sirolimus, teriflunomide or statins. There remains, however, an urgent need for treatments that protect against demyelination and axonal loss, or promote remyelination/regeneration. Due to the chronicity of MS, the therapeutic window for neuroprotective agents is wider than that following stroke or acute spinal cord injury, and may therefore allow the use of some drugs that have proven disappointing in other situations. Novel potential neuroprotective agents such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonists and ion-channel blockers will be entering Phase II trials in MS in the near future, and it is hoped that these agents will mark the start of a new era for DMTs for MS.
机译：现已广泛使用针对多发性硬化症（MS）的疾病改良疗法（DMT），并且其对复发率，磁共振成像结果以及在某些情况下与复发相关的残疾的有益作用已在众多临床研究中得到证实。但是，由于这些治疗仅能部分停止MS疾病进程，因此必须继续寻求改善的治疗方案和新疗法。改善我们的治疗性武器库的策略必须考虑该疾病发病机理的不同阶段或部分。可用的治疗方法可解决全身免疫功能障碍，血脑屏障通透性和中枢神经系统的炎症过程。目前，对一线DMT不能充分反应的患者通常被认为是使用细胞抑制剂或什至自体干细胞移植进行强化免疫抑制的候选人。然而，正在开发新的方法。联合疗法提供了一种替代方法，该方法可能具有提高治疗产量的巨大潜力，尽管可能在试验设计方面带来巨大挑战，但鉴于MS的复杂病理学，这无疑是合乎逻辑的一步。还正在开发几种新药，目的是提供对该疾病的炎性成分的更有效，方便和/或特异性调节。这些治疗方法包括人源化单克隆抗体，例如抗VLA-4抗体那他珠单抗，细胞内激活，信号传导途径和T细胞增殖的抑制剂，以及口服免疫调节剂，例如西罗莫司，特立氟胺或他汀类。然而，仍然迫切需要防止脱髓鞘和轴突丢失或促进髓鞘再生/再生的治疗。由于MS的长期性，神经保护剂的治疗窗口比中风或急性脊髓损伤后的治疗窗口宽，因此可能允许使用在其他情况下令人失望的某些药物。新型潜在的神经保护剂，例如α-氨基-3-羟基-5-甲基-4-异恶唑丙酸拮抗剂和离子通道阻滞剂，将在不久的将来进入MS的II期临床试验，希望这些药物能在MS DMT的新时代的开始。

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