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中枢神经系统疾病越来越严重的危害着人类的健康,由于血脑屏障上脑毛细血管内皮细胞的紧密连接,极大的限制了药物通过血液进入脑组织而发挥作用。目前所研发的传统脑部治疗性抗体临床Ⅲ期结果均不理想,究其原因主要由于抗体主动进入脑内的含量太低未能达到其治疗剂量,因此如何在疾病发现早期使抗体可以稳定、大量的进入血脑屏障(BBB)成为研究的关键。在众多使药物进入脑内的策略中利用血脑屏障自身的转运系统,通过与脑内腔表面特定受体结合经转胞吞作用来转运大分子的转运形式最具有开发前景。临床研究显示靶向转铁蛋白受体(TfR),胰岛素受体(IR)等的抗体可以有效促进药物跨血脑屏障进入脑内发挥作用。因此研发重组抗体成为了抗体治疗中枢神经系统疾病的研究趋势,将治疗性抗体与靶向脑部特异性受体的抗体相“组合”形成具有双功能的治疗性抗体,使其与血脑屏障上特定靶点结合进入脑内并在脑部达到治疗剂量从而发挥作用。文章对治疗脑部疾病的抗体,脑部靶点应用及其研究趋势进行综述。
Central nervous system diseases endanger human health more and more seriously, and due to the close connection of brain capillary endothelial cells on the blood-brain barrier, the drugs greatly limit the action of drugs entering the brain through blood. The clinical development of the current brain therapeutic antibody phase III clinical results are not ideal, the reason mainly due to the active antibody into the brain is too low to reach its therapeutic dose, so how to make the antibody early in the discovery of the disease can be stable, Massive entry into the blood-brain barrier (BBB) has become the key to research. Among the many strategies that allow drugs to enter the brain, the use of the blood-brain barrier’s own transport system, which transports transport of macromolecules through transcytosis through binding to specific receptors on the surface of the brain lumen, has the best prospect. Clinical studies have shown that antibodies targeting transferrin receptor (TfR), insulin receptor (IR) and the like can effectively promote the drug to enter the blood-brain barrier into the brain. Therefore, the development of recombinant antibodies has become the trend of antibodies in the treatment of central nervous system diseases. Therapeutic antibodies and antibodies targeting the brain-specific receptors are “combined” to form a dual-function therapeutic antibody that binds to the blood A specific target on the brain barrier binds into the brain and reaches a therapeutic dose in the brain to work. The article reviews the treatment of brain disease antibodies, brain target applications and research trends are reviewed.