期刊
NEUROPHARMACOLOGY
卷 120, 期 -, 页码 38-55出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2016.03.014
关键词
Blood-brain barrier; Alzheimer's disease; Therapeutic antibodies; Delivery
资金
- Pharma Research and Early Development (pRED), Neuroscience Discovery and Translation Area, Roche Innovation Center Basel, E Hoffmann-La Roche Basel, Switzerland
Therapeutic antibodies have essentially been banned from the central nervous system, and are so far limited to use mainly in multiple sclerosis. This is primarily due to the fact that antibody penetration across the blood brain barrier is very limited, with about only 0.1% of circulating antibodies estimated to reach the brain at steady-state concentration. Nonetheless, advances are being made with conventional antibodies, showing that minimal exposure can act centrally to mediate therapeutic effects. Immunotherapy in Alzheimer's disease is a noteworthy example where antibodies against amyloid-beta are able to reduce brain plaque pathology in preclinical models and humans. However, the advances in using antibodies directed at brain targets have also demonstrated impediments of low brain exposure in achieving clinical benefits, spurring increased attention in technologies designed to improve brain exposure of antibodies. Here we review antibodies in clinical trials for central nervous system disorders. Moreover, we describe some of the efforts to improve the therapeutic efficacy of antibodies by enhancing delivery across the blood brain barrier. This article is part of the Special Issue entitled Beyond small molecules for neurological disorders. (C) 2016 Elsevier Ltd. All rights reserved.
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