Development of a cell-penetrating peptide, transported retrogradely in the axon, for treatment of uncontrolled pain

• Project/Area Number: 19390408
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: University of Fukui
• Principal Investigator: HIROSE Munetaka University of Fukui, 医学部, 准教授 (50275228)
• Research Collaborator: MURATA Eri 福井大学, 医学部, 教務補佐員 ; UEDA Koyo 福井大学, 医学部, 大学院生 ; MA Weiying 福井大学, 医学部, 外国人研究者
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000); Fiscal Year 2009: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2008: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2007: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
• Keywords: 炎症性疼痛 / 細胞膜透過性ペプチド / 侵害受容性疼痛 / 神経障害性疼痛 / 神経成長因子 / 疼痛治療学 / TrkA / 慢性痛 / シグナル伝達 / 神経科学 / 蛋白質 / 薬学 / 痛み / 疼痛

Research Abstract

強い痛みに対して、現在の医学における治療方法は限られています。そこで、痛みを起こす物質の中の1つである神経成長因子の作用を抑制する、新しい薬物の開発が必要です。この研究では、神経成長因子の作用を抑制するペプチド(IPTRK3)を開発し、痛みの動物モデルを用いて、IPTRK3が強い痛みを抑えることを明らかにしました。IPTRK3は、新しい痛みの治療薬になるかもしれません。

Research Products

• [Journal Article] 慢性非がん性疼痛患者における嗜癖を予防するための長期オピオイド療法 (2010)
  • Author(s): 廣瀬宗孝、田畑麻里、坂井美賀子、関久美子、松木悠佳
  • Journal Title: ペインクリニック 31 Pages: 221-224
  • Peer Reviewed
• [Journal Article] 慢性非がん性痺痛患者における嗜癖を予防するための長期オピオイド療法 (2010)
  • Author(s): 廣瀬宗孝, 田畑麻里, 坂井美賀子, 関久美子, 松木悠佳
  • Journal Title: ペインクリニック 31 Pages: 221-224
  • Peer Reviewed
• [Journal Article] Local administration of synthetic cell-penetrating peptide antagonizing Trk A function suppresses inflammatory pain in rats (2010)
  • Author(s): K. Ueda, M. Hirose, E. Murata, M. Takatori, M. Ueda, H. Ikeda, K. Shigemi
  • Journal Title: J Pharmacol Sci Volume: 112 Pages: 438-443
  • Peer Reviewed
• [Journal Article] A synthetic cell-penetrating peptide antagonizing TrkA function suppresses neuropathic pain in mice (2010)
  • Author(s): Wei-Ying Ma, E. Murata, K. Ueda, Yoshihiro Kuroda, Ming-Hui Cao, Mineo Abe, K. Shigemi, M. Hirose
  • Journal Title: J Pharmacol Sci Volume: 114 Pages: 79-84
  • NAID: 10029889877
  • Peer Reviewed
• [Journal Article] 鎮痛補助薬が必要であった一例～疼痛コントロールに難渋した多発性骨髄腫～ (2009)
  • Author(s): 廣瀬宗孝
  • Journal Title: JPAP Ai 1 Pages: 6-6
• [Journal Article] Synthetic pentapeptides inhibiting autophosphorylation of insulin receptor in a non-ATP-competitive mechanism (2009)
  • Author(s): Kato M, Abe M, Kuroda Y, Hirose M, Nakano M, Handa T
  • Journal Title: J Pept Sci 15 Pages: 327-36
  • Peer Reviewed
• [Journal Article] Synthetic pentapeptides inhibiting autophosphorylation of insulin receptor in a non-ATP-comvetitive mechanism (2009)
  • Author(s): Kato M, Abe M, Kuroda Y, Hirose M, Nakano M, Handa T
  • Journal Title: J Pept Sci 15 Pages: 327-336
  • Peer Reviewed
• [Journal Article] Inhibition of autophosphorylation of epidermal growth factor receptor by a small peptide not employing an ATP-competitive mechanism (2008)
  • Author(s): Abe M, Kuroda Y, Hirose M, Kato M, Murakami M, Watanabe Y, Nakano M, Handa T
  • Journal Title: Biopolymers 89 Pages: 40-51
  • Peer Reviewed
• [Journal Article] General anaesthesia and TrkA mRNA in peripheral blood mononuclear cells (2008)
  • Author(s): Tsugita K, Hirose M, Murata E, Iho S.
  • Journal Title: Eur J Anaesthesiol 25 Pages: 1032-1033
• [Journal Article] Cluster headache with Brugada electrocardiogram pattern (2008)
  • Author(s): Matsuki Y, Hirose M, Nakano A, Sarasawa K, Hamada T.
  • Journal Title: J Headache Pain 9 Pages: 249-251
  • Peer Reviewed
• [Journal Article] Effect of synthetic cell-penetrating peptide on TrkA activity in PC12 cells (2008)
  • Author(s): Hirose M, Takatori M, Kuroda Y, Abe M, Murata E, Isada T, Ueda K, Shigemi K, Shibazaki M, Shimizu F, Hirata M, Fukazawa K, Sakaguchi M, Kageyama K, Tanaka Y.
  • Journal Title: J Pharmacol Sci 106 Pages: 107-113
  • NAID: 10024317682
  • Peer Reviewed
• [Journal Article] Cluster headache with Brugada electrocardiogram pattern (2008)
  • Author(s): Matsuki Y, Hirose M, et al.
  • Journal Title: J Headache Pain 9 Pages: 249-251
  • Peer Reviewed
• [Journal Article] Inhibition of autophosphorylation of epidermal growth factor receptor by a small peptide not employing an ATP-competitive mechanism (2008)
  • Author(s): Abe M, Kuroda Y, Hirose M, et al.
  • Journal Title: Biopolymers 89 Pages: 40-51
  • Peer Reviewed
• [Journal Article] Effect of synthetic cell-penetrating peptide on TrkA activity in PC12 cells (2008)
  • Author(s): Hirose, M
  • Journal Title: J Pharmacological Sciences 106 Pages: 107-113
  • NAID: 10024317682
  • Peer Reviewed
• [Journal Article] 慢性非がん性疼痛患者におけるオピオイドによる嗜癖 (2007)
  • Author(s): 廣瀬宗孝、重見研司、細川豊史、深澤圭太
  • Journal Title: ペインクリニック 28 Pages: 1511-1514
  • Peer Reviewed
• [Journal Article] 慢性非がん性疼痛患者におけるオピオイドによる嗜癖 (2007)
  • Author(s): 廣瀬宗孝
  • Journal Title: ペインクリニック 28 Pages: 1511-1514
  • Peer Reviewed
• [Presentation] IPTRK3 for cancer pain therapy (2010)
  • Author(s): M. Hirose
  • Organizer: BIO 2010
  • Place of Presentation: シカゴ(アメリカ)
  • Year and Date: 2010-05-03 – 2010-05-06
• [Presentation] がん性疼痛治療薬の開発-炎症性疼痛モデルにおける細胞膜透過性TrkA活性抑制ペプチドの効果 (2009)
  • Author(s): 上田康陽、廣瀬宗孝、上田雅史、重見研司
  • Organizer: 日本麻酔科学会第56回学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2009-08-16
• [Presentation] Neuropathic painの症状から予測するガバペンチンの臨床効果 (2009)
  • Author(s): 廣瀬宗孝、坂井美賀子、松木悠佳
  • Organizer: 日本ペインクリニック学会第43回大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-07-18
• [Presentation] Neuropathic pain の症状から予測するガバペンチンの臨床効果 (2009)
  • Author(s): 廣瀬宗孝, 坂井美賀子, 松木悠佳
  • Organizer: 日本ペインクリニック学会第43回大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-07-18
• [Presentation] 肢端紅痛症と考えられた1症例 (2008)
  • Author(s): 廣瀬宗孝
  • Organizer: 第1回福井疼痛懇話会
  • Place of Presentation: 福井
  • Year and Date: 2008-10-10
• [Presentation] TrkAキナーゼ活性を抑制する細胞膜透過性合成ペプチドによる疼痛治療薬の開発 (2008)
  • Author(s): 廣瀬宗孝、上田康陽、清水久美子、次田佳代、松木悠佳、重見研司
  • Organizer: 日本麻酔科学会第55回学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2008-06-12
• [Presentation] A novel synthetic cell-penetrating peptide directly inhibits TrkA activity and suppresses heat hyperalgesia caused by nerve growth factor (2008)
  • Author(s): Hirose M, Ueda K, Murata E, Kuroda Y, Abe M, Shimizu K, Tsugita K, Matsuki Y, Shigemi K
  • Organizer: 13th International Pain Clinic Congress, World Society of Pain Clinicians 2008
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2008-05-31
• [Presentation] A novel synthetic cell-penetrating peptide directly inhibits TrkA activity and suppresses heat hyperalgesia caused by nerve growth factor (2008)
  • Author(s): Hirose M, et al.
  • Organizer: 13th International Pain Clinic Congress, Worid Society of Pain Clinicians 2008
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2008-05-31
• [Presentation] 慢性非がん性疼痛における神経因性疼痛に対するリン酸コデインの効果 (2008)
  • Author(s): 廣瀬宗孝、坂井美賀子、松木悠佳、佐藤倫祥、清水久美子、次田佳代、三田建一郎、信川泰成、田畑麻里、石本雅幸、上田雅史、重見研司
  • Organizer: 日本ペインクリニック学会第15回北陸地方会
  • Place of Presentation: 金沢
  • Year and Date: 2008-03-15
• [Presentation] Synthetic Peptide Inhibiting TrkA Activity Suppresses Long-Lasting Hyperalgesia Induced by NGF (2007)
  • Author(s): Hirose M, Takatori M, Kuroda Y, Abe M, Shibazaki M
  • Organizer: Annual Meeting of American Society of Anesthesiologists
  • Place of Presentation: San Francisco, U.S. A
  • Year and Date: 2007-10-15
• [Presentation] Synthetic peptide inhibiting TrkA activity suppresses long-lasting hyperalgesia induced by NGF (2007)
  • Author(s): Hirose, M
  • Organizer: Annual Meeting of American Society of Anesthesiologists
  • Place of Presentation: San Francisco
  • Year and Date: 2007-10-15
• [Presentation] 慢性非がん性疼痛に対するオピオイド治療における嗜癖の評価 (2007)
  • Author(s): 廣瀬宗孝、細川豊史、深澤圭太
  • Organizer: 日本ペインクリニック学会第41回大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-07-07
• [Presentation] 逆行性軸索輸送を利用した細胞膜透過性合成ペプチドによる疼痛の中枢性感作の抑制 (2007)
  • Author(s): 廣瀬宗孝、高取真由美、柴崎雅志、阪口雅洋、影山京子、田中義文
  • Organizer: 日本麻酔科学会第54回学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2007-05-31
• [Patent(Industrial Property Rights)] 合成ペプチドを用いた良性および悪性腫瘍治療薬 (2008)
  • Inventor(s): 廣瀬宗孝黒田義弘
  • Industrial Property Rights Holder: 福井大学
  • Acquisition Date: 2008-06-25
• [Patent(Industrial Property Rights)] 合成ペプチドを用いた良性および悪性腫瘍治療薬 (2008)
  • Inventor(s): 廣瀬宗孝, 黒田義弘
  • Industrial Property Rights Holder: 福井大学
  • Filing Date: 2008-06-25