Development of Biomimetic DDS to improve healthy longevity and its application to the treatment for sarcopenia
Project/Area Number |
20K21485
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 47:Pharmaceutical sciences and related fields
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Research Institution | Kumamoto University |
Principal Investigator |
Maruyama Toru 熊本大学, 大学院生命科学研究部(薬), 教授 (90423657)
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Co-Investigator(Kenkyū-buntansha) |
渡邊 博志 熊本大学, 大学院生命科学研究部(薬), 准教授 (70398220)
前田 仁志 熊本大学, 大学院生命科学研究部(薬), 助教 (80791483)
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Project Period (FY) |
2020-07-30 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2020: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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Keywords | サルコペニア / 健康寿命 / ミオスタチン / アルブミン / ドラッグデリバリーシステム / バイオミメティック / 筋萎縮因子 / アルブミン融合技術 / チオレドキシン / グレリン / sActRIIB / バイオミメティクDDS |
Outline of Research at the Start |
健康長寿社会を実現するためには健康寿命の延伸が必須であり、そのためには“サルコペニア”対策が鍵を握る。本研究では、筋萎縮阻害因子のバイオミメティックな薬物送達システム(DDS)を開発し、4種類の筋萎縮モデル動物を用いて有用性を評価する。筋萎縮阻害因子としては、チオレドキシン、グレリン、sActRⅡB(筋萎縮因子ミオスタチン阻害剤)の3種類を選択するとともに、血中滞溜性に富み、筋組織への移行性も高い一酸化窒素付加ヒト血清アルブミンダイマーをDDS担体として用いる。本ハイブリッド融合体はバイオミメティックDDSとして、優れた筋萎縮抑制・筋力維持作用を発揮することが期待される。
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Outline of Final Research Achievements |
pDNA fused with HSA dimer and muscle atrophy inhibitor was prepared, and then the fusion protein was expressed in yeast, and purified by several chromatographic methods. Then, an S-nitroso compound was prepared with isoamyl nitrite. We examined the pharmacokinetics of the fusion protein in mice and found that the retention in blood significantly increased and the muscle distribution was significantly enhanced compared with the muscular atrophy inhibitor alone. We also evaluated the pharmacological effect of the fusion protein against muscle atrophy model animals and found that the decrease in body weight and skeletal muscle weight was significantly suppressed, and the muscle strength and muscular endurance were recovered compared with the saline group.
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Academic Significance and Societal Importance of the Research Achievements |
本研究成果は廃用症候群の予防など他の疾患治療へも応用可能である。例えば、癌に代表される消耗性疾患の場合、カヘキシアと呼ばれる骨格筋萎縮を呈し、 QOLの低下はもとより予後を悪化させる。カヘキシアは高頻度でサルコペニアを合併するため、本融合体の開発はカヘキシア対策にも有望である。加えて、宇宙空間では、重力の低下に伴い、筋委縮や筋力低下が生じやすくなり、5~11日間の滞在で約20%程度の筋肉が減少する。そのため、近い将来に実現する宇宙時代では、この筋肉萎縮・筋力消失への対策も切望されているが、サルコペニア治療薬の開発はこれら宇宙科学への貢献も期待できる。
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Report
(3 results)
Research Products
(20 results)
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[Journal Article] Cysteinylated albumin as a potential biomarker for the progression of kidney disease in patients with type 2 diabetes2021
Author(s)
Imafuku T, Watanabe H, Oniki K, Yoshida A, Kato H, Nakano T, Tokumaru K, Fujita I, Arimura N, Maeda H, Sakamoto Y, Kondo N, Morita A, Saruwatari J, Tanaka M, Matsushita K, Wada T, Fukagawa M, Otagiri M, Fitzgerald ML, Jinnouchi H, Maruyama T.
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Journal Title
Diabetes Care
Volume: 26
Issue: 6
Pages: e115-e117
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] An acute phase protein alfa1-acid glycoprotein mitigates AKI and its progression to CKD through its anti-inflammatory action2021
Author(s)
Hiroshi Watanabe*,#, Rui Fujimura*, Yuto Hiramoto*, Ryota Murata, Kento Nishida, Jing Bi, Tadashi Imafuku, Hisakazu Komori, Hitoshi Maeda, Ayumi Mukunoki, Toru Takeo, Naomi Nakagata, Motoko Tanaka, Kazutaka Matsushita, Masafumi Fukagawa, Toru Maruyama# *equal contribution; #equal correspondence
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Journal Title
Sci Rep.
Volume: 12;11(1)
Issue: 1
Pages: 7953-7953
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Reduction-responsive and multi-drug deliverable albumin nanoparticles: an antitumor drug to Abraxane_ against human pancreatic tumor-bearing mice2021
Author(s)
Naoki Hirakawa, Yu Ishima, Ryo Kinoshita, Ryuto Nakano, Victor Tuan Giam Chuang, Hidenori Ando, Taro Shimizu, Keiichiro Okuhira, Toru Maruyama, Masaki Otagiri, Tatsuhiro Ishida
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Journal Title
ACS Applied Bio Materials
Volume: 268
Issue: 5
Pages: 4302-4309
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Reduction-responsive and multi-drug deliverable albumin nanoparticles: an antitumor drug to Abraxane_ against human pancreatic tumor-bearing mice2021
Author(s)
Naoki Hirakawa, Yu Ishima, Ryo Kinoshita, Ryuto Nakano, Victor Tuan Giam Chuang, Hidenori Ando, Taro Shimizu, Keiichiro Okuhira, Toru Maruyama, Masaki Otagiri, Tatsuhiro Ishida
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Journal Title
ACS Applied Bio Materials
Volume: 4,5
Pages: 4302-4309
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Indoxyl sulfate contributes to adipose tissue inflammation through the activation of NADPH oxidase2020
Author(s)
Shoma Tanaka*, Hiroshi Watanabe*,#, Takehiro Nakano, Tadashi Imafuku, Hiromasa Kato, Kai Tokumaru, Nanaka Arimura, Yuki Enoki, Hitoshi Maeda, Motoko Tanaka, Kazutaka Matsushita, Masafumi Fukagawa, Toru Maruyama# *equal contribution; #equal correspondence
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Journal Title
Toxins (Basel)
Volume: 5;12(8):
Issue: 8
Pages: 502-502
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Development of a long acting FGF21 analogue-albumin fusion protein and its anti-diabetic effects2020
Author(s)
Hiroshi Watanabe*,#, Masako Miyahisa*, Mayuko Chikamatsu*, Kento Nishida, Yuki Minayoshi, Mei Takano, Shota Ichimizu, Yoshihiro Kobashigawa, Hiroshi Morioka, Hitoshi Maeda, Toru Maruyama# *equal contribution; #equal correspondence
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Journal Title
J Control Release
Volume: 10;324:
Pages: 522-531
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Advanced oxidation protein products contribute to renal tubulopathy via perturbation of renal fatty acids2020
Author(s)
Imafuku, T., Watanabe, H., Satoh, T., Matsuzaka, T., Inazumi, T., Kato, H., Tanaka, S., Nakamura, Y., Nakano, T., Tokumaru, K., Maeda, H., Tanaka, M., Matsushita, K., Tsuchiya, S., Sugimoto, Y., Shimano, H., Fukagawa, M., and Maruyama, T.
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Journal Title
Kidney360
Volume: 1
Issue: 8
Pages: 781-796
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Changes in redox state of albumin before and after kidney transplantation in patients with end-stage renal disease2020
Author(s)
Ryota Tanaka, Tadashi Imafuku, Yosuke Suzuki, Kento Nishida, Kotaro Matsusaka, Toshitaka Shin, Yuhki Sato, Yu Ishima, Hiroshi Watanabe, Hiromitsu Mimata, Toru Maruyama, Hiroki Itoh
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Journal Title
Clin Biochem
Volume: 81
Pages: 20-26
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] In vivo evaluation of drug dialyzability in a rat model of hemodialysis.2020
Author(s)
Fukunaga M, Kadowaki D, Mori M, Hagiwara S, Narita Y, Saruwatari J, Tanaka R, Watanabe H, Yamasaki K, Taguchi K, Ito H, Maruyama T, Otagiri M, Hirata S.
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Journal Title
PLoS One
Volume: 15
Issue: 6
Pages: 20-26
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The<I> DsbA-L</I> gene is associated with respiratory function of the elderly via its adiponectin multimeric or antioxidant properties.2020
Author(s)
Kentaro Oniki, Hirofumi Nohara, Ryunosuke Nakashima, Yui Obata, Narumi Muto, Yuki Sakamoto, Keiko Ueno-Shuto, Tadashi Imafuku, Yu Ishima, Hiroshi Watanabe, Toru Maruyama, Koji Otake, Yasuhiro Ogata, Mary Ann Suico, Hirofumi Kai, Tsuyoshi Shuto, and Junji Saruwatari.
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Journal Title
Scientific Reports
Volume: 10
Issue: 1
Pages: 5973-5973
DOI
Related Report
Peer Reviewed / Open Access
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