New therapeutic approach using functional copper complexes to treat Menkes disase.

• Project/Area Number: 25461534
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: Munakata Mitsutoshi 東北大学, 医学(系)研究科(研究院), 非常勤講師 (30312573)
• Co-Investigator(Kenkyū-buntansha): KODAMA Hiroko 帝京大学, 医学部, 非常勤講師 (00093386) ; 菊池 敦生 東北大学, 大学病院, 助教 (30447156)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: Menkes病 / macular mouse / Ｍｅｎｋｅｓ病 / 銅錯体 / 銅補充療法 / Macular mouse

Outline of Final Research Achievements

Menkes disease is a severe X-chromosome-linked disorder caused by mutations in a copper transporter, ATP7A. We investigated the oral copper supplementation with Cu-gtsm, a lipophilic copper complex, in male hemizygous macular mice, an animal model of Menkes disease. Orally administered Cu-gtsm rescued affected mice with an increase of cerebral copper concentration and activities of cerebral Cu-dependent enzymes including cytochrome oxidase and dopamine-β-hydroxylase. Serum ceruloplasmin activities were also recovered. However, rotarod test performance was still impaired. This study indicates that Cu-gtsm potentially have clinical utility as an oral medication in the treatment of Menkes disease.

Research Products

• [Journal Article] Development of a Therapeutic Agent for Menkes Disease: Solubilization of a Copper-Disulfiram Complex (2015)
  • Author(s): 星佑次郎、谷紀彦、田畑英嗣、若松真太朗、宗形光敏、丸山一雄、児玉浩子、忍足鉄太、夏苅英昭、高橋秀依
  • Journal Title: YAKUGAKU ZASSHI Volume: 135 Issue: 3 Pages: 493-499
  • DOI: 10.1248/yakushi.14-00188
  • NAID: 130004756516
  • ISSN: 0031-6903, 1347-5231
  • Year and Date: 2015-03-01
  • Peer Reviewed
• [Journal Article] Elevated serum levels of neutrophil elastase in patients with influenza virus-associated encephalopathy. (2015)
  • Author(s): Sun G, Ota C, Kitaoka S, Chiba Y, Takayanagi M, Kitamura T, Yamamoto K, Fujie H, Mikami H, Uematsu M, Hino-Fukuyo N, Munakata M, Kure S, Haginoya K.
  • Journal Title: J Neurol Sci. Volume: 349 Pages: 190-195
  • Peer Reviewed
• [Journal Article] Reduction in glutamine/glutamate levels in the cerebral cortex after adrenocorticotropic hormone therapy in patients with west syndrome. (2014)
  • Author(s): Munakata M, Togashi N, Sakamoto O, Haginoya K, Kobayashi Y, Onuma A, Iinuma K, Kure S.
  • Journal Title: Tohoku J Exp Med. Volume: 232 Pages: 277-283
  • NAID: 130004460120
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Menkes病治療薬としての銅錯体の創出 (2013)
  • Author(s): ペク・スンア，星祐次郎，谷 紀彦，田畑英嗣， 関むつみ，鈴木 亮，丸山一雄，宗形光敏，廣木伴子，児玉浩子，夏苅英昭，高橋秀依
  • Organizer: 第57回 日本薬学会関東支部大会
  • Place of Presentation: 板橋、東京
• [Presentation] Studies on Cu complexes as therapeutic drugs for Menkes disease (2013)
  • Author(s): Hideyo Takahashi, Paiku Soong-a, Yujiro Hoshi, Norihiko Tani, Hideaki Natsugari, Mutsumi Seki, Ryo Suzuki, Kazuo Maruyama, Mitsutoshi Munakata, Tomoko Hiroki, Hiroko Kodama
  • Organizer: The 10th conference for ISTERH (international society for trace element research in humans)
  • Place of Presentation: 東京