Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Expert Opin Biol Ther. 2016 Jun;16(6):827-839. doi: 10.1517/14712598.2016.1158809. Epub 2016 Mar 10.
Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating disease of the CNS and results in neurological disability. Existing immunomodulatory and immunosuppressive approaches lower the number of relapses but do not cure or reverse existing deficits nor improve long-term disability in MS patients.
Monogenic antibodies were described as treatment options for MS, however the immunogenicity of mouse antibodies hampered the efficacy of potential therapeutics in humans. Availability of improved antibody production technologies resulted in a paradigm shift in MS treatment strategies. In this review, an overview of immunotherapies for MS that use conventional monoclonal antibodies reactive to immune system and their properties and mechanisms of action will be discussed, including recent advances in MS therapeutics and highlight natural autoantibodies (NAbs) that directly target CNS cells.
Recent challenges for MS therapy are the identification of relevant molecular and cellular targets, time frame of treatment, and antibody toxicity profiles to identify safe treatment options for MS patients. The application of monoclonal antibody therapies with better biological efficacy associated with minimum side effects possesses huge clinical potential. Advances in monoclonal antibody technologies that directly target cells of nervous system may promote the CNS regeneration field from bench to bedside.
多发性硬化症(MS)是最常见的中枢神经系统慢性炎症性脱髓鞘疾病,导致神经功能障碍。现有的免疫调节和免疫抑制方法可以降低复发次数,但不能治愈或逆转现有缺陷,也不能改善 MS 患者的长期残疾状况。
单基因抗体被描述为 MS 的治疗选择,但是鼠源抗体的免疫原性阻碍了潜在治疗药物在人类中的疗效。改进的抗体生产技术的出现,使 MS 治疗策略发生了范式转变。在这篇综述中,我们将讨论用于 MS 的免疫疗法,这些疗法使用常规的单克隆抗体来靶向免疫系统及其特性和作用机制,包括 MS 治疗的最新进展,并强调直接针对中枢神经系统细胞的天然自身抗体(NAbs)。
MS 治疗的最新挑战是确定相关的分子和细胞靶点、治疗时间框架以及抗体毒性特征,以确定 MS 患者的安全治疗选择。具有最小副作用的与更好的生物学疗效相关的单克隆抗体治疗的应用具有巨大的临床潜力。直接靶向神经系统细胞的单克隆抗体技术的进步可能会促进从实验室到临床的中枢神经系统再生领域。