Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montréal, QC, Canada.
Front Immunol. 2019 Jul 19;10:1657. doi: 10.3389/fimmu.2019.01657. eCollection 2019.
Neuroinflammation is a prominent pathological feature of all neuroimmunological diseases, including, but not limited to, multiple sclerosis (MS), myasthenia gravis, neuromyelitis optica, and Guillain-Barré syndrome. All currently-approved therapies for the treatment of these diseases focus on controlling or modulating the immune (innate and adaptive) responses to limit demyelination and neuronal damage. The primary purpose of this review is to detail the pre-clinical data and proposed mechanism of action of novel drugs currently in clinical trial, with a focus on novel compounds that promote repair and regeneration in the central nervous system (CNS). As the most recent advances have been made in the field of MS research, this review will focus primarily on this disease and its animal models. However, these compounds are likely to be effective for a range of indications with a neuroinflammatory component. Traditionally, MS was thought to proceed through two distinct phases. The first, predominantly inflammatory stage, is characterized by acute episodes of clinical relapse, followed by periods of partial or total recovery with an apparent absence of overall disease progression. In the vast majority of patients, this relapsing-remitting disease subsequently progresses into a second more chronic, neurodegenerative phase, which is characterized by oligodendrocyte damage and axonal destruction leading to brain atrophy and an accumulation of disability. Recent work has shown that rather than occurring independently, both the inflammatory and degenerative phases may run concurrently. This, combined with evidence that early therapeutic intervention slows accumulation of disability and delays progression, highlights the need for novel therapeutic approaches that promote repair and regeneration early in the disease trajectory. Such compounds may be used as monotherapies or in conjunction with classical anti-inflammatory therapies. This review will highlight novel therapies currently in clinical trial, and likely to appear in clinical practice in the near future, focusing on compounds that target the immune system and/or enhance endogenous repair mechanisms in the CNS.
神经炎症是所有神经免疫性疾病的突出病理特征，包括但不限于多发性硬化症 (MS)、重症肌无力、视神经脊髓炎和吉兰-巴雷综合征。目前所有批准用于治疗这些疾病的疗法都侧重于控制或调节免疫（先天和适应性）反应，以限制脱髓鞘和神经元损伤。本综述的主要目的是详细介绍目前处于临床试验阶段的新型药物的临床前数据和拟议作用机制，重点介绍促进中枢神经系统 (CNS) 修复和再生的新型化合物。由于最近在 MS 研究领域取得了最新进展，本综述将主要关注该疾病及其动物模型。然而，这些化合物可能对具有神经炎症成分的一系列适应症有效。传统上，MS 被认为经历两个不同阶段。第一阶段主要是炎症期，其特征是临床复发的急性发作，随后是部分或完全恢复的时期，总体疾病进展似乎不存在。在绝大多数患者中，这种缓解-复发疾病随后进展为第二更慢性、神经退行性阶段，其特征是少突胶质细胞损伤和轴突破坏，导致脑萎缩和残疾积累。最近的工作表明，炎症和退行性阶段可能不是独立发生的，而是同时发生的。这一点，加上早期治疗干预可减缓残疾积累并延迟进展的证据，强调了需要新型治疗方法，以在疾病轨迹的早期促进修复和再生。这些化合物可以单独使用或与经典抗炎疗法联合使用。本综述将重点介绍目前处于临床试验阶段、可能在不久的将来在临床实践中出现的新型疗法，重点关注针对免疫系统和/或增强中枢神经系统内源性修复机制的化合物。
