| Download | - View final version: Grabody B, an IGF1 receptor-based shuttle, mediates efficient delivery of biologics across the blood-brain barrier (PDF, 6.9 MiB)
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| DOI | Resolve DOI: https://doi.org/10.1016/j.crmeth.2022.100338 |
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| Author | Search for: Shin, Jung-Won; Search for: An, SungwonORCID identifier: https://orcid.org/0000-0001-8828-1908; Search for: Kim, Dongin; Search for: Kim, Hyunjoo; Search for: Ahn, Jinhyung; Search for: Eom, Jaehyun; Search for: You, Weon-Kyoo; Search for: Yun, Hyesu; Search for: Lee, Bora; Search for: Sung, Byungje; Search for: Jung, JinwonORCID identifier: https://orcid.org/0000-0002-7981-3316; Search for: Kim, SehyunORCID identifier: https://orcid.org/0000-0003-0291-6058; Search for: Son, Yonggyu; Search for: Sung, Eunsil; Search for: Lee, Hanbyul; Search for: Lee, Suyeon; Search for: Song, DaehaeORCID identifier: https://orcid.org/0000-0003-4367-3793; Search for: Pak, Youngdon; Search for: Sandhu, Jagdeep K.1; Search for: Haqqani, Arsalan S.1; Search for: Stanimirovic, Danica B.1; Search for: Yoo, Jiseon; Search for: Kim, Donghwan; Search for: Maeng, SunghoORCID identifier: https://orcid.org/0000-0002-9347-7902; Search for: Lee, JeonghunORCID identifier: https://orcid.org/0000-0002-1584-9301; Search for: Lee, Sang Hoon |
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| Affiliation | - National Research Council of Canada. Human Health Therapeutics
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| Funder | Search for: University of California, San Diego; Search for: National Rehabilitation Center |
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| Format | Text, Article |
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| 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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| Publication date | 2022-11-21 |
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| Publisher | Elsevier |
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| Licence | |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| Identifier | S2667237522002351 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | 3f5e5729-5782-4b0a-b959-0e2072d307a7 |
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| Record created | 2023-12-13 |
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| Record modified | 2023-12-13 |
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