Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

Drug delivery

New targets for drug delivery across the BBB

Nature Reviews Drug Discovery volume 15, pages 84–85 (2016)Cite this article

Subjects

A monolayer of brain endothelial cells (BECs), supported by astrocytes and pericytes, restricts the transfer of proteins between the blood and the brain, such that only ∼0.1% of circulating antibodies cross the intact BBB. RMT, whereby a ligand or antibody binds to a receptor expressed at the luminal surface of BECs and is transported to the brain parenchyma via the endocytic machinery, is a physiological route that has been explored as a potential mechanism for CNS drug delivery. Notably, targeting the transferrin receptor (TFR) has shown promise, but safety concerns have limited the application of this approach in humans.

For the current study, Watts and co-workers first investigated the commonly studied RMT targets low-density lipoprotein receptor-related protein 1 (LRP1) and insulin receptor (IR). Previous studies showed enrichment of mRNA transcripts encoding these receptors in BECs relative to lung and liver endothelial cells. The team used flow-assisted cell sorting to isolate antibodies specific to the murine target and used radiolabelling to assess cortical localization and brain uptake of the antibodies after intravenous dosing in mice.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Zuchero, Y. J. et al. Discovery of novel blood–brain barrier targets to enhance brain uptake of therapeutic antibodies. Neuron 89, 70–82 (2016)

    Article  CAS  Google Scholar 

Download references

Authors
  1. Katie Kingwell
    View author publications

    You can also search for this author in PubMed Google Scholar

Related links

Related links

Related links in Nature Research

Banks, W. A. From blood–brain barrier to blood–brain interface: new opportunities for CNS drug delivery. Nat. Rev. Drug Discov. (2016)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kingwell, K. New targets for drug delivery across the BBB. Nat Rev Drug Discov 15, 84–85 (2016). https://doi.org/10.1038/nrd.2016.14

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrd.2016.14

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research