Roles of IGF1 signaling in age-related hearing impairment

• Project/Area Number: 26462557
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Kyoto University
• Principal Investigator: Nakagawa Takayuki 京都大学, 医学研究科, 講師 (50335270)
• Co-Investigator(Kenkyū-buntansha): 山本 典生 京都大学, 医学研究科, 講師 (70378644) ; 岡野 高之 京都大学, 医学研究科, 助教 (60642931)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 内耳 / 加齢性難聴 / インスリン様細胞増殖因子１ / 感音難聴

Outline of Final Research Achievements

In the present study, we investigated roles of IGF-1 signaling in the onset of age-related hearing impairment aiming drug development for age-related hearing impairment. We analyzed ages of the onset of age-related hearing impairment in three mouse strains, which have different mechanisms and timing for age-related hearing impairment by means of physiological and morphological assessments. Thereafter, changes in mRNA levels of IGF-1 signaling associated molecules just before the onset of age-related hearing impairment were examined using q-PCR. As results, we determined ages when age-related hearing impairment appear in three strains, and identified changing expression patterns of molecules associated with IGF-1 signaling at the onset of age-related hearing impairment in C57BL6 mice.

Research Products

• [Journal Article] Activation of IGF1 Signaling in the Cochlea Induces the Transcription of Its Mediators During the Protection of Cochlear Hair Cells Against Aminoglycoside. (2017)
  • Author(s): Hayashi Y, Yamamoto N, Nakagawa T, Omori K, Ito J.
  • Journal Title: Otol Neurotol. Volume: 38 Issue: 2 Pages: 278-282
  • DOI: 10.1097/mao.0000000000001276
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Netrin 1 mediates protective effects exerted by insulin-like growth factor 1 on cochlear hair cells. (2017)
  • Author(s): Yamahara K, Nakagawa T, Ito J, Kinoshita K, Omori K, Yamamoto N.
  • Journal Title: Neuropharmacology. Volume: 119 Pages: 26-39
  • DOI: 10.1016/j.neuropharm.2017.03.032
  • Peer Reviewed
• [Journal Article] Prognostic impact of salvage treatment on hearing recovery in patients with sudden sensorineural hearing loss refractory to systemic corticosteroids: A retrospective observational study (2015)
  • Author(s): Nakagawa, T. Yamamoto, M. Kumakawa, K. Usami, S. I. Hato, N. Tabuchi, K. Takahashi, M. Fujiwara, K. Sasaki, A. Komune, S. Yamamoto, N. Hiraumi, H. Sakamoto, T. Shimizu, A. Ito, J.
  • Journal Title: Auris Nasus Larynx Volume: Online Issue: 5 Pages: 1-6
  • DOI: 10.1016/j.anl.2015.12.004
  • NAID: 130006880794
  • Peer Reviewed
• [Journal Article] Insulin-like growth factor 1: A novel treatment for the protection or regeneration of cochlear hair cells (2015)
  • Author(s): Yamahara, K. Yamamoto, N. Nakagawa, T. Ito, J.
  • Journal Title: Hear Res Volume: 330 Pages: 2-9
  • DOI: 10.1016/j.heares.2015.04.009
  • Peer Reviewed
• [Journal Article] A randomized controlled clinical trial of topical insulin-like growth factor-1 therapy for sudden deafness refractory to systemic corticosteroid treatment. (2014)
  • Author(s): Nakagawa T, Kumakawa K, Usami S, Hato N, Tabuchi K, Takahashi M, Fujiwara K, Sasaki A, Komune S, Sakamoto T, Hiraumi H, Yamamoto N, Tanaka S, Tada H, Yamamoto M, Yonezawa A, Ito-Ihara T, Ikeda T, Shimizu A, Tabata Y, Ito J.
  • Journal Title: BMC Med Volume: 12 Pages: 219-219
  • NAID: 120005517912
  • Peer Reviewed / Open Access
• [Journal Article] Application of insulin-like growth factor-1 in the treatment of inner ear disorders (2014)
  • Author(s): Yamamoto, N. Nakagawa, T. Ito, J.
  • Journal Title: Frontiers in pharmacology Volume: 5 Pages: 208-208
  • DOI: 10.3389/fphar.2014.00208
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Strategies for developing novel therapeutics for sensorineural hearing loss. (2014)
  • Author(s): Nakagawa T
  • Journal Title: Front Pharmacol Volume: 5 Pages: 206-206
  • DOI: 10.3389/fphar.2014.00206
  • Peer Reviewed / Open Access
• [Presentation] IGF-1 Effects for Hair Cell Protection Against Neomycin is Mediated by Paracrine of Netrin-1 in Supporting Cells (2017)
  • Author(s): Takayuki Nakagawa, Kohei Yamahara, Norio Yamamoto, Juichi Ito, Koichi Omori
  • Organizer: 40th Mid-Winter Meeting for Association for Research in Otolaryngology
  • Place of Presentation: Baltimore, MD, USA
  • Year and Date: 2017-02-11
  • Int'l Joint Research
• [Presentation] Netrin 1 is a mediator of IGF-1 protective effects on cochlear hair cells (2016)
  • Author(s): Takayuki Nakagawa, Kohei Yamahara, Norio Yamamoto, Juichi Ito, Koichi Omori
  • Organizer: 53rd Workshop on Inner Ear Biology 2016
  • Place of Presentation: Montpellier, France
  • Year and Date: 2016-09-17
  • Int'l Joint Research
• [Presentation] Topical IGF-1 therapy for sensorineural hearing loss (2016)
  • Author(s): Takayuki Nakagawa, Norio Yamamoto, Takayuki Okano, Kohei Yamahara, Juichi Ito, Koichi Omori
  • Organizer: 16th JAPAN KOREA Joint Meeting of Otorhinolaryngology-Head and Neck Surgery
  • Place of Presentation: Hyatt Regency（Tokyo, Japan）
  • Year and Date: 2016-03-29
  • Int'l Joint Research
• [Presentation] Potential of IGF-1 for restoration of synaptic contacts between inner hair cells and spiral ganglion neurons (2016)
  • Author(s): Takayuki Nakagawa, Nakarin Asaka, Tomoko Kita, Risa Tona, Norio Yamamoto, Juichi Ito, Koichi Omori
  • Organizer: 10th International tinnitus research initiative conference
  • Place of Presentation: Nottingham, UK
  • Year and Date: 2016-03-16
  • Int'l Joint Research
• [Presentation] Clinical application of IGF-1 for treatment of hearing loss (2015)
  • Author(s): Nakagawa T
  • Organizer: Ageing, neurodegeneration and hearing loss: an IGF-1 signalling perspective
  • Place of Presentation: Madrid, Spain
  • Year and Date: 2015-12-10
  • Int'l Joint Research / Invited
• [Presentation] 組織工学を用いた聴覚再生医療 (2015)
  • Author(s): 中川隆之
  • Organizer: 第36回日本炎症・再生医学会
  • Place of Presentation: 虎ノ門ヒルズフォーラム（東京都）
  • Year and Date: 2015-07-21
• [Presentation] Topical IGF-1 therapy as salvage treatment for sudden deafness (2015)
  • Author(s): Nakagawa T
  • Organizer: 30th Politzer Society Meeting 1st World Congress of Otology
  • Place of Presentation: TOKI MESSE（Niigata, Japan）
  • Year and Date: 2015-07-01
  • Int'l Joint Research
• [Presentation] 難治性突発性難聴例における2次治療の選択を含めた聴力予後関連因子に関する多変量解析 (2015)
  • Author(s): 中川隆之、坂本達則、平海晴一、山本典生、伊藤壽一
  • Organizer: 第116回日本耳鼻咽喉科学会総会
  • Place of Presentation: 東京国際フォーラム（東京都）
  • Year and Date: 2015-05-20
• [Presentation] A Randomized Controlled Clinical trial of Topical IGF-1 Therapy via Gelatin Hydrogels for Refractory Sudden Sensorineural Hearing Loss. (2015)
  • Author(s): Nakagawa T, Kumakawa K, Usami S, Hato N, Tabuchi K, Takahashi M, Fujiwara K, Sasaki A, Komune S, Sakamoto T, Hiraumi H, Yamamoto N, Tanaka S, Tada H, Yamamoto M, Yonezawa A, Ito-Ihara T, Ikeda T, Shimizu A, Tabata Y, Ito J
  • Organizer: ARO 38th Annual MidWinter Meeting
  • Place of Presentation: Baltimore MA USA
  • Year and Date: 2015-02-21 – 2015-02-25
• [Presentation] 突発性難聴に対するゼラチンハイドロゲルを用いたIGF-1局所投与の有効性 (2014)
  • Author(s): 中川隆之、坂本達則、山本典生、平海晴一、伊藤壽一、佐々木亮、田渕経司、熊川孝三、 宇佐美真一、高橋真理子、藤原敬三、羽藤直人、小宗静男
  • Organizer: 第24回日本耳科学会総会・学術講演会
  • Place of Presentation: 朱鷺メッセ（新潟市）
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] Topical IGF-1 therapy using a gelatin hydrogel: pre-clinical study, clinical trials, and mechanisms (2014)
  • Author(s): Nakagawa T
  • Organizer: 51st Inner Ear Biology Workshop
  • Place of Presentation: Sheffield, UK
  • Year and Date: 2014-08-30 – 2014-09-02
  • Invited
• [Presentation] 突発性難聴に対するIGF1局所投与有効性に関するランダム化対照試験 (2014)
  • Author(s): 中川隆之、坂本達則、平海晴一、山本典生、熊川孝三、宇佐美真一、羽藤直人、田渕経司、村上信五、内藤 泰、佐々木亮、小宗静男、伊藤壽一
  • Organizer: 第115回日本耳鼻咽喉科学会総会・学術講演会
  • Place of Presentation: ヒルトン福岡シーホーク（福岡市）
  • Year and Date: 2014-05-14 – 2014-05-17
• [Book] Regeneration Medicine for the Inner Ear (2014)
  • Author(s): Nakagawa T
  • Total Pages: 15
  • Publisher: Springer Japan KK