2019 Fiscal Year Research-status Report
Developing brain-penetrating anti-inflammatory nano-medicines to treat neurodegenerative diseases
| Project/Area Number |
18K14100
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| Research Institution | Kawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine |
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Principal Investigator |
ゴンザレスカーター ダニエル 公益財団法人川崎市産業振興財団(ナノ医療イノベーションセンター), ナノ医療イノベーションセンター, 研究員 (80800903)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | BBB penetration |
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| Outline of Annual Research Achievements |
We have successfully employed the glucose-decorated nanomicelles to efficiently deliver proteins into the brain. We have shown this system delivers antibody fragments (Fabs) against amyloid-beta protein, resulting in reduced amyloid-beta plaque burden in mouse models of Alzheimer's disease. This work has been published in ACS Nano (doi:doi.org/10.1021/acsnano.9b09991)
We have also developed a new brain targeting strategy to increase the brain specificity of nanoparticle delivery which exploits the high impermeability of the blood-brain barrier itself to generate the required brain-specific targets. This work will be published in the journal PNAS and a patent application has been submitted to protect the intellectual property.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
In addition to the glucose-decorated nanoparticle delivery system originally outlined in the Kakenhi research project, we were inspired to develop a new brain-targeting system which does not require blood-glucose levels to be modulated, thereby allowing a more smooth transition into the clinic. The work outlining the proof of principle of this strategy has been completed and will be published in the journal Proceedings of the National Academy of Sciences of America.
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| Strategy for Future Research Activity |
The work on delivering anti-inflammatory proteins (namely CD200) into the brain as a therapeutic strategy against neurodegenerative diseases will be ongoing.
In addition, work will be carried out the optimise the new targeting strategy (which relies on specific brain target generation) and further develop it for clinical translation.
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| Causes of Carryover |
End of project research, including anti-inflammatory therapeutic delivery with current brain targeting strategy and optimisation of novel brain targeting strategy to allow therapy delivery in future projects.
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Research Products
(3 results)
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[Journal Article] Dual-Sensitive Nanomicelles Enhancing Systemic Delivery of Therapeutically Active Antibodies Specifically into the Brain2020
Author(s)
Jinbing Xie, Daniel Gonzalez-Carter, Theofilus A. Tockary, Noriko Nakamura, Yonger Xue, Makoto Nakakido, Hiroki Akiba, Anjaneyulu Dirisala, Xueying Liu, Kazuko Toh, Tao Yang, Zengtao Wang, Shigeto Fukushima, Junjie Li, Sabina Quader, Kouhei Tsumoto, Takanori Yokota, Yasutaka Anraku*, and Kazunori Kataoka
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Journal Title
ACS Nano
Volume: -
Pages: -
DOI
Peer Reviewed / Int'l Joint Research
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