Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
Department of Neurology, National Institute of Neurology and Neurosurgery, Mexico City, Mexico.
Curr Opin Neurol. 2019 Jun;32(3):378-384. doi: 10.1097/WCO.0000000000000692.
Medications for relapsing multiple sclerosis (MS) effectively reduce relapse rate, mitigate disability progression and improve MRI measures of inflammation. However, they have virtually no impact on remyelination which is the major mechanism preventing MS-associated neurodegeneration. Stimulating the generation of myelin-(re)producing cells is therefore a central focus of current MS research and a yet unmet clinical need. Here, we present and evaluate key scientific studies from the field of (therapeutic) remyelination research covering the past 1.5 years.
On the one hand, recent research in the field of remyelination has strongly focused on repurposing drugs that are already approved for other indications by the Food and Drug Administration or the European Medicines Agency. On the other hand, emerging agents such as the mAbs opicinumab and GNbAC1 target entirely new and unconventional pathways. Some of them have already been tested in clinical trials in which they were found to exert beneficial effects on remyelination as well as on neuroregeneration/neuroprotection.
Several of the agents discussed in this review have shown a high potential as future neuroregenerative drugs. However, future trials with more sensitive clinical and paraclinical primary endpoints will be necessary to prove their effectiveness in MS.
用于治疗复发型多发性硬化症（MS）的药物可有效降低复发率，减缓残疾进展，并改善 MRI 炎症指标。然而，它们对髓鞘再生几乎没有影响，而髓鞘再生是防止 MS 相关神经退行性变的主要机制。因此，刺激髓鞘（再）生成细胞的产生是当前 MS 研究的核心焦点，也是尚未满足的临床需求。在此，我们介绍和评估了过去 1.5 年中（治疗性）髓鞘再生研究领域的关键科学研究。
一方面，髓鞘再生领域的最新研究强烈关注重新利用已被美国食品和药物管理局或欧洲药品管理局批准用于其他适应症的药物。另一方面，新兴药物如单抗 opicinumab 和 GNbAC1 则针对全新的、非常规的途径。其中一些药物已经在临床试验中进行了测试，结果表明它们对髓鞘再生以及神经再生/神经保护具有有益作用。
本文讨论的几种药物具有作为未来神经再生药物的巨大潜力。然而，未来需要进行更敏感的临床和临床前主要终点试验，以证明它们在 MS 中的有效性。
