Developing brain-penetrating anti-inflammatory nano-medicines to treat neurodegenerative diseases

2019 年度 実施状況報告書

• 研究課題/領域番号: 18K14100
• 研究機関: 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)
• 研究代表者: 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)
• 研究期間 (年度): 2018-04-01 – 2021-03-31
• キーワード: BBB penetration

研究実績の概要

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.

現在までの達成度 (区分)

2: おおむね順調に進展している

理由

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.

今後の研究の推進方策

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.

次年度使用額が生じた理由

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.

研究成果

• [雑誌論文] Dual-Sensitive Nanomicelles Enhancing Systemic Delivery of Therapeutically Active Antibodies Specifically into the Brain (2020)
  • 著者名/発表者名: 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
  • 雑誌名: ACS Nano 巻: - ページ: -
  • DOI: doi.org/10.1021/acsnano.9b09991
  • 査読あり / 国際共著
• [学会発表] Targeting nanoparticles to the brain by exploiting the blood-brain barrier impermeability to selectively label the brain endothelium (2020)
  • 著者名/発表者名: Gonzalez-Carter, Daniel
  • 学会等名: Nanobio2020 (post-poned due to Coronavirus)
  • 招待講演
• [産業財産権] Japan patent office (2020)
  • 発明者名: Gonzalez Carter Daniel
  • 権利者名: Gonzalez Carter Daniel
  • 産業財産権種類: 特許
  • 産業財産権番号: 2020-055478