a Department of Neurology , Mayo Clinic College of Medicine and Science , Rochester , MN , USA.
b Medical Scientist Training Program , Mayo Clinic College of Medicine and Science , Rochester , MN , USA.
Expert Opin Biol Ther. 2018 May;18(5):545-560. doi: 10.1080/14712598.2018.1441284. Epub 2018 Feb 25.
Multiple sclerosis (MS) is a chronic and progressive inflammatory demyelinating disease of the human central nervous system (CNS) and is the most common disabling neurological condition in young adults, resulting in severe neurological defects. No curative or long-term progression-inhibiting therapy has yet been developed. However, recent investigation has revealed potential strategies that do not merely modulate potentially pathogenic autoimmune responses, but stimulate remyelination within CNS lesions.
We discuss the history and development of natural human IgM-isotype immunoglobulins (HIgMs) and recently-identified aptamer-conjugates that have been shown to enhance endogenous myelin repair in animal models of demyelination by acting on myelin-producing oligodendrocytes (OLs) or oligodendrocyte progenitor cells (OPCs) within CNS lesions. We also discuss future development aims and applications for these important novel technologies.
Aptamer conjugate Myaptavin-3064 and recombinant human IgM-isotype antibody rHIgM22 regenerate CNS myelin, thereby reducing axonal degeneration and offering the potential of recovery from MS relapses, reversal of disability and prevention of disease progression. Advancement of these technologies into the clinic for MS treatment is therefore a top priority. It remains unclear to what extent the therapeutic modalities of remyelinating antibodies and aptamers may synergize with other currently-approved therapies to yield enhanced therapeutic effects.
多发性硬化症(MS)是一种慢性且进行性的人类中枢神经系统(CNS)炎症脱髓鞘疾病,是年轻人中最常见的致残性神经疾病,导致严重的神经缺陷。目前还没有开发出治愈或长期抑制疾病进展的疗法。然而,最近的研究揭示了一些潜在的策略,这些策略不仅可以调节潜在的致病性自身免疫反应,还可以刺激中枢神经系统病变内的髓鞘修复。
我们讨论了天然人 IgM 同种型免疫球蛋白(HIgMs)的历史和发展,以及最近发现的适体缀合物,这些缀合物已被证明通过作用于中枢神经系统病变中的髓鞘产生少突胶质细胞(OLs)或少突胶质前体细胞(OPCs),可以增强脱髓鞘动物模型中的内源性髓鞘修复。我们还讨论了这些重要新技术的未来发展目标和应用。
适体缀合物 Myaptavin-3064 和重组人 IgM 同种型抗体 rHIgM22 可再生中枢神经系统髓鞘,从而减少轴突变性,并有可能从 MS 复发中恢复、逆转残疾和预防疾病进展。因此,将这些技术推进到 MS 治疗的临床应用是当务之急。尚不清楚髓鞘再生抗体和适体的治疗方式在多大程度上可以与其他目前批准的治疗方法协同作用,以产生增强的治疗效果。