Finke John M, Banks William A
Division of Sciences and Mathematics, Interdisciplinary Arts and Sciences, University of Washington Tacoma, Tacoma, WA, USA.
Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA.
Hum Antibodies. 2017;25(3-4):131-146. doi: 10.3233/HAB-160306.
This review serves to highlight approaches that may improve the access of antibody drugs to regions of the brain affected by Alzheimer's Disease. While previous antibody drugs have been unsuccessful in treating Alzheimer's disease, recent work demonstrates that Alzheimer's pathology can be modified if these drugs can penetrate the brain parenchyma with greater efficacy. Research in antibody blood-brain barrier drug delivery predominantly follows one of three distinct directions: (1) enhancing influx with reduced antibody size, addition of Trojan horse modules, or blood-brain barrier disruption; (2) modulating trancytotic equilibrium and/or kinetics of the neonatal Fc Receptor; and (3) manipulation of antibody glycan carbohydrate composition. In addition to these topics, recent studies are discussed that reveal a role of glycan sialic acid in suppressing antibody efflux from the brain.
本综述旨在强调可能改善抗体药物进入受阿尔茨海默病影响的脑区的方法。虽然先前的抗体药物在治疗阿尔茨海默病方面未取得成功，但最近的研究表明，如果这些药物能够更有效地穿透脑实质，阿尔茨海默病的病理状态是可以改变的。抗体血脑屏障药物递送的研究主要遵循三个不同方向之一：（1）通过减小抗体大小、添加特洛伊木马模块或破坏血脑屏障来增强内流；（2）调节新生儿Fc受体的转胞吞平衡和/或动力学；（3）操纵抗体聚糖碳水化合物组成。除了这些主题外，还讨论了最近的研究，这些研究揭示了聚糖唾液酸在抑制抗体从脑内流出中的作用。
