Drug-diagnostic co-development in Tropical Medicine, combating Human African Trypanosomiasis

• Project/Area Number: 18KK0454
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
• Allocation Type: Multi-year Fund
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Osaka City University
• Principal Investigator: Kido Yasutoshi 大阪市立大学, 大学院医学研究科, 准教授 (90511395)
• Project Period (FY): 2019 – 2021
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
• Keywords: トリパノソーマ症 / 顧みられない熱帯病 / アフリカトリパノソーマ症 / ヒトアフリカトリパノソーマ症 / 人獣共通感染症 / アフリカ睡眠病 / アスコフラノン / シアン耐性酸素呼吸 / 中枢神経感染動物モデル / 分子マーカー探索 / 薬剤開発 / 熱帯感染症（マラリア、エボラ出血熱） / トランスレーショナルリサーチ

Outline of Final Research Achievements

We have succeeded in establishing an animal model that mimics the human chronic phase of human African trypanosomiasis, which is one of the Neglected Tropical Diseases that human beings should control. In therapeutic experiments with Ascofuranone and its derivatives, AF was effective even in the chronic model using clinical isolates. Furthermore, it has been known that AF is sensitized in the presence of glycerol, clarifying that glycerol increased the sensitivity by changing protozoan energy metabolism.

Academic Significance and Societal Importance of the Research Achievements

人類が制圧すべき感染症の1つであるヒトアフリカトリパノソーマ症のヒト慢性期疾患に対する新規医薬品候補を見出した。本研究は、流行地である海外でのみ実施可能な研究であり、新規医薬品候補の報告は、今後の感染症対策にとって重要な一歩となる。また、本研究の遂行には、日本とコンゴ民主共和国の両国の若手研究者が多く従事した。感染流行に即応できる研究者育成にも貢献することとなった。

Research Products

• [Int'l Joint Research] Institut Nacional Recherche Biomedicale(INRB), 国立生物医学研究所(コンゴ民主共和国) (2019)
• [Journal Article] Evaluation of Cryptosporidium parvum oocyst inactivation following exposure to ultraviolet light-emitting diodes by in vitro excystation and dye staining assays (2022)
  • Author(s): Matsubayashi Makoto、Teramoto Isao、Urakami Itsuo、Naohara Jun、Sasai Kazumi、Kido Yasutoshi、Kaneko Akira
  • Journal Title: Parasitology International Volume: 88 Pages: 102557-102557
  • DOI: 10.1016/j.parint.2022.102557
  • Peer Reviewed
• [Journal Article] Inflammatory cardiomyopathy of possibly overlapping aetiology: a case posing treatment dilemma and potential association (2021)
  • Author(s): Nakagama Shun、Candray Katherine、Yamamoto Tasuku、Tsugeno Yuta、Nakagama Yu、Kido Yasutoshi、Nitahara Yuko、Maejima Yasuhiro、Sasano Tetsuo
  • Journal Title: ESC Heart Failure Volume: 9 Issue: 1 Pages: 761-765
  • DOI: 10.1002/ehf2.13771
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Assessment of the diagnostic accuracy and relevance of a novel ELISA system developed for seroepidemiologic surveys of Helicobacter pylori infection in African settings (2021)
  • Author(s): Tshibangu-Kabamba Evariste、Phuc Bui Hoang、Tuan Vo Phuoc、Kayiba Nadine Kalenda、Rosas-Aguirre Angel、Devleesschauwer Brecht、Cimuanga-Mukanya Alain、Ngoma Kisoko Patrick de Jsus、Disashi Ghislain Tumba、Mumba Ngoyi Dieudonn、Kido Yasutoshi、Speybroeck Niko、Yamaoka Yoshio
  • Journal Title: PLOS Neglected Tropical Diseases Volume: 15 Issue: 9 Pages: e0009763-e0009763
  • DOI: 10.1371/journal.pntd.0009763
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Biochemical Studies of Mitochondrial Malate: Quinone Oxidoreductase from Toxoplasma gondii (2021)
  • Author(s): Acharjee Rajib、Talaam Keith、Hartuti Endah、Matsuo Yuichi、Sakura Takaya、Gloria Bundutidi、Hidano Shinya、Kido Yasutoshi、Mori Mihoko、Shiomi Kazuro、Sekijima Masakazu、Nozaki Tomoyoshi、Umeda Kousuke、Nishikawa Yoshifumi、Hamano Shinjiro、Kita Kiyoshi、Inaoka Daniel
  • Journal Title: International Journal of Molecular Sciences Volume: 22 Issue: 15 Pages: 7830-7830
  • DOI: 10.3390/ijms22157830
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Toxoplasma Infection Induces Sustained Up-Regulation of Complement Factor B and C5a Receptor in the Mouse Brain via Microglial Activation: Implication for the Alternative Complement Pathway Activation and Anaphylatoxin Signaling in Cerebral Toxoplasmosis (2021)
  • Author(s): Shinjyo N, Hikosaka K, Kido Y, Yoshida H, Norose K.
  • Journal Title: Front Immunol. Volume: 11 Pages: 603924-603924
  • DOI: 10.3389/fimmu.2020.603924
  • NAID: 120007000273
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of ultraviolet light-emitting diodes (UV-LED) at four different peak wavelengths against Cryptosporidium parvum oocysts by inactivation assay using immunodeficient mice (2020)
  • Author(s): Takahashi Karin、Matsubayashi Makoto、Ohashi Yukio、Naohara Jun、Urakami Itsuo、Sasai Kazumi、Kido Yasutoshi、Kaneko Akira、Teramoto Isao
  • Journal Title: Parasitology International Volume: 77 Pages: 102108-102108
  • DOI: 10.1016/j.parint.2020.102108
  • Peer Reviewed
• [Journal Article] Therapeutic targeting of mitochondrial ROS ameliorates murine model of volume overload cardiomyopathy. (2019)
  • Author(s): Okamura K, Nakagama Y, Takeda N, Soma K, Sato T, Isagawa T, Kido Y, Sakamoto M, Manabe I, Hirata Y, Komuro I, Ono M
  • Journal Title: Journal of Pharmacological Sciences Volume: 141 Issue: 1 Pages: 56-63
  • DOI: 10.1016/j.jphs.2019.09.005
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of a novel Helicobacter pylori East Asian-type CagA ELISA for detecting patients infected with various cagA genotypes (2019)
  • Author(s): Doohan D, Miftahussurur M, Matsuo Y, Kido Y, Akada J, Matsuhisa T, Yee TT, Htet K, Aftab H, Vilaichone RK, Mahachai V, Ratanachu-Ek T, Tshering L, Waskito LA, Fauzia KA, Uchida T, Syam AF, Rezkitha YAA, Yamaoka Y
  • Journal Title: Med Microbiol Immunol Volume: 209(1) Pages: 29-40
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Discovery of trypanocidal coumarins with dual inhibition of both the glycerol kinase and alternative oxidase of Trypanosoma brucei brucei. (2019)
  • Author(s): Balogun EO, Inaoka DK, Shiba T, Tsuge C, May B, Sato T, Kido Y, Nara T, Aoki T, Honma T, Tanaka A, Inoue M, Matsuoka S, Michels PAM, Watanabe YI, Moore AL, Harada S, Kita K.
  • Journal Title: FASEB J Volume: 33 Issue: 11 Pages: 13002-13013
  • DOI: 10.1096/fj.201901342r
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Complete biosynthetic pathways of ascofuranone and ascochlorin in Acremonium egyptiacum (2019)
  • Author(s): Araki Yasuko、Awakawa Takayoshi、Matsuzaki Motomichi、Cho Rihe、Matsuda Yudai、Hoshino Shotaro、Shinohara Yasutomo、Yamamoto Masaichi、Kido Yasutoshi、Inaoka Daniel Ken、Nagamune Kisaburo、Ito Kotaro、Abe Ikuro、Kita Kiyoshi
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 未定 Issue: 17 Pages: 8269-8274
  • DOI: 10.1073/pnas.1819254116
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Insights into the ubiquinol/dioxygen binding and proton relay pathways of the alternative oxidase (2019)
  • Author(s): Shiba Tomoo、Inaoka Daniel Ken、Takahashi Gen、Tsuge Chiaki、Kido Yasutoshi、Young Luke、Ueda Satoshi、Balogun Emmanuel Oluwadare、Nara Takeshi、Honma Teruki、Tanaka Akiko、Inoue Masayuki、Saimoto Hiroyuki、Harada Shigeharu、Moore Anthony L.、Kita Kiyoshi
  • Journal Title: Biochimica et Biophysica Acta (BBA) - Bioenergetics Volume: 1860 Issue: 5 Pages: 375-382
  • DOI: 10.1016/j.bbabio.2019.03.008
  • Peer Reviewed / Int'l Joint Research
• [Presentation] シアン耐性呼吸を標的とした抗トリパノソーマ症薬の早期臨床開発計画 (2021)
  • Author(s): 加来 奈津子, 中釜 悠, 仁田原 裕子, 道向 優, 稲岡 健ダニエル, 山本 雅一, 斎本 博之, 上村 尚人, 金子 明, 北 潔, 城戸 康年
  • Organizer: 日本寄生虫学会・日本臨床寄生虫学会合同大会
• [Presentation] アカデミア創薬:独創的な創薬研究者達の挑戦 コンゴ民主共和国拠点での新興・再興感染症創薬 (2020)
  • Author(s): 城戸 康年, 中釜 悠, 上村 尚人, Mumba Dieudonne, Muyembe Jean-Jacques
  • Organizer: 臨床薬理学会総会
  • Invited
• [Presentation] シャーガス慢性心筋炎の病態形成機構 (2020)
  • Author(s): 中釜 悠, 伊藤 正道, 仁田原 裕子, Candray Katherine, Rodriguez Stanley, 武田 憲彦, 嶋田 淳子, 金子 明, 城戸 康年
  • Organizer: 日本小児循環器学会
• [Presentation] グローバルヘルス課題克服にむけたコンゴ民主共和国におけるトランスレーショナルリサーチ拠点の形成 (2019)
  • Author(s): 城戸 康年, 中釜 悠, 仁田原 裕子, 北 潔, Mumba Dieudonne, Muyembe JeanJacques, 金子 明, 上村 尚人
  • Organizer: 臨床薬理学会総会
• [Presentation] アフリカトリパノソーマ症治療薬開発に向けた、First in Human試験の立案・実施への取り組み (2019)
  • Author(s): 中釜 悠, 城戸 康年, 仁田原 裕子, 中谷 大作, 北 潔, 上村 尚人
  • Organizer: 臨床薬理学会総会