Diagnosis and remedy for mitochondria-related nephropathy

• Project/Area Number: 18H02822
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Tohoku University
• Principal Investigator: Takaaki Abe 東北大学, 医工学研究科, 教授 (80292209)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
• Keywords: ミトコンドリア関連腎症 / MA-5 / GDF15 / PET / ミトコンドリア腎症 / 診断と治療 / GDF-15 / ミトコンドリア病 / インドール化合物 / ATP / ミトコンドリアダイナミクス / ミトコンドリア / ミトコンドリア関連腎疾患 / Mitochonic acid 5（MA-5） / ミトフィリン / ミトコンドリアROS / 新規マーカー

Outline of Final Research Achievements

Mitochondrial disease is one kind of intractable disease for which the diagnosis is still complicated by the distinct lack of sensitive and specific biomarkers and remedies.We reported that a new indole-derivative drug, MA-5, improved the cardiac and renal respiration and prolonged survival in diseas model mice carrying a deleted mitochondrial DNA mutation that makes it suitable for evaluating the phenotype of human mitochondrial diseases and renal diseases. In addition, mitochondrial disease is one kind of intractable disease for which the diagnosis is still complicated by the distinct lack of sensitive and specific biomarkers.
We found the potential biomarkers for mitochondrial dysfunction to improve diagnoses and develop new medicines to ameliorate the mitochondrial diseases.

Academic Significance and Societal Importance of the Research Achievements

本研究によりミトコンドリア機能異常の診断が容易となり、患を早期に予見してその抑制・予防に利用される社会が実現される。またミトコンドリアと疾患の関連が明らかになり、AKI、シスプラチン腎症だけ無くミトコンドリア関連腎症であるAKIや虚血性腎症に用いる治療法の開発に役に立つと考えられた。

Research Products

• [Int'l Joint Research] NIH(米国)
• [Int'l Joint Research] 台湾大学(その他の国・地域（台湾）)
• [Int'l Joint Research] ハーバード大学(米国)
• [Journal Article] Canagliflozin reduces plasma uremic toxins and alters the intestinal microbiota composition in a chronic kidney disease mouse model (2018)
  • Author(s): Mishima Eikan、Fukuda Shinji、Kanemitsu Yoshitomi、Saigusa Daisuke、Mukawa Chikahisa、Asaji Kei、Matsumoto Yotaro、Tsukamoto Hiroki、Tachikawa Tatsuki、Tsukimi Tomoya、Fukuda Noriko N、Ito Sadayoshi、Soga Tomoyoshi、Tomioka Yoshihisa、Abe Takaaki
  • Journal Title: Am J Physiol Renal Physiol Volume: 印刷中 Issue: 4 Pages: 824-833
  • DOI: 10.1152/ajprenal.00314.2017
  • Peer Reviewed / Open Access
• [Journal Article] Focal Segmental Glomerulosclerosis Associated with Chronic Progressive External Ophthalmoplegia and Mitochondrial DNA A3243G Mutation. (2018)
  • Author(s): Narumi K, Mishima E, Akiyama Y, Matsuhashi T, Nakamichi T, Kisu K, Nishiyama S, Ikenouchi H, Kikuchi A, Izumi R, Miyazaki M, Abe T, Sato H, Ito S
  • Journal Title: Nephron Volume: 138 Issue: 3 Pages: 243-248
  • DOI: 10.1159/000485109
  • Peer Reviewed
• [Journal Article] Crossroads of metabolism and CKD. (2018)
  • Author(s): Suzuki T, Abe T.
  • Journal Title: Kidney Int. Volume: 94 Issue: 2 Pages: 242-243
  • DOI: 10.1016/j.kint.2018.03.023
  • Peer Reviewed
• [Presentation] Gut microbiota and chronic kidney diseases (2018)
  • Author(s): Takaaki ABE
  • Organizer: 20th Human Genome Meeting 2018
  • Int'l Joint Research / Invited
• [Presentation] 胞ストレスから見た腎障害の分子機構 (2018)
  • Author(s): 阿部高明
  • Organizer: 第91日本内分泌学会学術集会
  • Invited
• [Presentation] 高血圧とその合併症発症における多臓器連関 (2018)
  • Author(s): 阿部高明
  • Organizer: 第41回高血圧学会
  • Invited
• [Presentation] ミトコンドリアと皮膚疾患 (2018)
  • Author(s): 阿部高明
  • Organizer: 第34回日本臨床皮膚科医会総会
  • Invited
• [Presentation] 腸腎連関 (2018)
  • Author(s): 阿部高明
  • Organizer: 第8回日本腎臓リハビリテーション学会学術集会
  • Invited