Article ; Online: Grabody B, an IGF1 receptor-based shuttle, mediates efficient delivery of biologics across the blood-brain barrier.
Cell reports methods
2022 Volume 2, Issue 11, Page(s) 100338
Abstract: Effective delivery of therapeutics to the brain is challenging. Molecular shuttles use receptors expressed on brain endothelial cells to deliver therapeutics. Antibodies targeting transferrin receptor (TfR) have been widely developed as molecular ... ...
| Abstract | Effective delivery of therapeutics to the brain is challenging. Molecular shuttles use receptors expressed on brain endothelial cells to deliver therapeutics. Antibodies targeting transferrin receptor (TfR) have been widely developed as molecular shuttles. However, the TfR-based approach raises concerns about safety and developmental burden. Here, we report insulin-like growth factor 1 receptor (IGF1R) as an ideal target for the molecular shuttle. We also describe Grabody B, an antibody against IGF1R, as a molecular shuttle. Grabody B has broad cross-species reactivity and does not interfere with IGF1R-mediated signaling. We demonstrate that administration of Grabody B-fused anti-alpha-synuclein (α-Syn) antibody induces better improvement in neuropathology and behavior in a Parkinson's disease animal model than the therapeutic antibody alone due to its superior serum pharmacokinetics and enhanced brain exposure. The results indicate that IGF1R is an ideal shuttle target and Grabody B is a safe and efficient molecular shuttle. |
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| MeSH term(s) | Animals ; Blood-Brain Barrier/metabolism ; Biological Products/metabolism ; Endothelial Cells/metabolism ; Brain/metabolism ; Biological Transport ; Antibodies/metabolism |
| Chemical Substances | Biological Products ; Antibodies |
| Language | English |
| Publishing date | 2022-11-21 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ISSN | 2667-2375 |
| ISSN (online) | 2667-2375 |
| DOI | 10.1016/j.crmeth.2022.100338 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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