Development of a renal carbon monoxide delivery system for treatment of lethal rhabdomyolysis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02604
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: Kumamoto University
• Principal Investigator: Maruyama Toru 熊本大学, 大学院生命科学研究部(薬), 教授 (90423657)
• Co-Investigator(Kenkyū-buntansha): 渡邊 博志 熊本大学, 大学院生命科学研究部(薬), 准教授 (70398220) ; 前田 仁志 熊本大学, 大学院生命科学研究部(薬), 助教 (80791483)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 一酸化炭素 / バイオミメティック / 赤血球 / 細胞療法 / 急性腎障害

Outline of Final Research Achievements

Severe rhabdomyolysis, which occurs in disasters and accidents, often complicates with acute kidney injury (AKI), leading to a fatal case of multiple organ failure. Thus, the development of drugs that improve the prognosis is eagerly desired. “Carbon monoxide (CO)” from renal heme oxygenase (HO)-1, which is activated by rhabdomyolysis-induced AKI, plays an important role as a stress response defense mechanism in kidney. In the present study, to develop a new therapeutic agent for rhabdomyolysis-induced AKI, we created a CO-releasing nano-formulation, that can be used in various situations such as disasters, using hemoglobin as a CO-carrier. We further loaded a renal-oriented peptide to the formulation and developed a "renal CO delivery system". Finally, we demonstrated its preventive and therapeutic effect using rhabdomyolysis model animals.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

“クラッシュ症候群”は外傷性横紋筋融解症の一つである。阪神大震災や福知山列車事故など、本邦のように災害や事故が多発する状況下では、横紋筋融解症AKIに対する治療法の開発は重要かつ急務であるが、医療機関だけでなく、災害現場でも使用可能で予後を改善する有効な治療法は存在せず、現行では輸液や頻回な血液透析等の対処療法に留まっている。申請者は、熊本地震に被災した際に、この点を強く実感した。本邦のような災害・事故多発国において、横紋筋融解症の予後改善を企図とした薬剤を開発する意義は高い。