Abstract: TH-PO041
Therapeutic Efficacy of FEx-022 in Protecting the Kidneys during Ischemia-Reperfusion Injury
Session Information
- AKI: Epidemiology, Risk Factors, and Prevention - 1
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 101 AKI: Epidemiology, Risk Factors, and Prevention
Authors
- Kim, Sung ki, Massachusetts General Hospital, Boston, Massachusetts, United States
- Kim, Jayoung, Chungnam National University, Daejeon, Korea (the Republic of)
- Stiles, Wesley Robert, Massachusetts General Hospital, Boston, Massachusetts, United States
- Lee, Hee Young, Naason Science Inc, Osong-eup, Korea (the Republic of)
- Park, Kyung Ho, Naason Science Inc, Osong-eup, Korea (the Republic of)
- Park, Larry C., Naason Science Inc, Osong-eup, Korea (the Republic of)
- Kang, Min-Woong, Chungnam National University, Daejeon, Korea (the Republic of)
- Choi, Hak Soo, Massachusetts General Hospital, Boston, Massachusetts, United States
Background
Acute kidney injury (AKI) is a common yet critical clinical problem, significantly increasing the morbidity and mortality of patients, particularly in critical care settings. AKI is characterized by a sudden decline in kidney function, leading to the accumulation of waste products in the blood, an imbalance in body fluids, and potential progression to chronic kidney disease. Despite the prevalence and severity of AKI, there is currently no approved or effective treatment available in the clinic. In a previous study with rhabdomyolysis-induced AKI model, a novel polymer-drug conjugate, FEx-022, demonstrated kidney protection and ameliorated glomerular filtration rate (GFR) by two-fold compared to the negative control. In this study, we further evaluated the effectiveness of FEx-022, using an ischemia-reperfusion injury (IRI) AKI model.
Methods
FEx-022 was prepared in large scale for in vitro and in vivo assays. In the following study, mice were divided into four groups: sham control, IRI with vehicle, IRI with reference drug, and IRI with FEx-022. Plasma and urine samples were collected to analyze plasma creatinine, blood urea nitrogen (BUN), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and GFR. Survival rates, kidney histology, and inflammatory cytokines are also evaluated.
Results
In this study, FEx-022 demonstrated kidney protection, measured in various parameters such as survival rate and GFR. Other analysis will provide deeper insights on the compound’s ability to suppress reactive oxygen species (ROS) damage and cell death biomarkers, primarily through the inhibition of ferroptosis.
Conclusion
FEx-022 exhibits therapeutic effects in the IRI-AKI model, which demonstrates that FEx-022 can protect kidneys in AKI. Our findings suggest that FEx-022 could be a potential candidate as a novel therapeutic targeting AKI, offering a promising avenue to address a critical unmet need in nephrology.
Funding
- Commercial Support – Ferrex Therapeutics, Inc.