Journal
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 55
Volume 55, Issue -, Pages 613-631Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-pharmtox-010814-124852
Keywords
blood-brain barrier; biologics; receptor-mediated transport; antibody; transferrin receptor; insulin receptor; low density lipoprotein receptor
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Funding
- NHGRI NIH HHS [T32 HG002760] Funding Source: Medline
- NIGMS NIH HHS [T32 GM008349] Funding Source: Medline
- NINDS NIH HHS [R01 NS071513] Funding Source: Medline
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Biologics are an emerging class of medicines with substantial promise to treat neurological disorders such as Alzheimer's disease, stroke, and multiple sclerosis. However, the blood-brain barrier (BBB) presents a formidable obstacle that appreciably limits brain uptake and hence the therapeutic potential of biologics following intravenous administration. One promising strategy for overcoming the BBB to deliver biologics is the targeting of endogenous receptor-mediated transport (RMT) systems that employ vesicular trafficking to transport ligands across the BBB endothelium. If a biologic is modified with an appropriate targeting ligand, it can gain improved access to the brain via RMT. Various RMT-targeting strategies have been developed over the past 20 years, and this review explores exciting recent advances, emphasizing studies that show brain targeting in vivo.
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