Abstract: FR-PO0657
SCO-792, an Enteropeptidase Inhibitor, Slows Development of Renal and Hepatic Cysts in a Mouse Model of ADPKD
Session Information
- Cystic Kidney Diseases: Basic and Translational Research
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Kawamura, Takuro, Department of Rheumatology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
- Hattanda, Fumihiko, Department of Hemodialysis and Apheresis, Hokkaido University Hospital, Sapporo, Hokkaido, Japan
- Takenaka, Shun, Department of Rheumatology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
- Watanabe-Kusunoki, Kanako, Department of Rheumatology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
- Sugama, Jun, SCOHIA PHARMA, Inc, Fujisawa, Kanagawa, Japan
- Moritoh, Yusuke, SCOHIA PHARMA, Inc, Fujisawa, Kanagawa, Japan
- Watanabe, Masanori, SCOHIA PHARMA, Inc, Fujisawa, Kanagawa, Japan
- Nakazawa, Daigo, Department of Rheumatology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
- Atsumi, Tatsuya, Department of Rheumatology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
- Nishio, Saori, Department of Hemodialysis and Apheresis, Hokkaido University Hospital, Sapporo, Hokkaido, Japan
Background
Excessive intake of branched-chain amino acids has been shown to activate the mammalian target of the rapamycin (mTOR) pathway, leading to disease progression of autosomal dominant polycystic kidney disease (ADPKD). SCO-792, an enteropeptidase inhibitor, reduces amino acids absorption by inhibiting the enzymatic conversion of dietary proteins into absorbable amino acids. This study evaluates whether SCO-792 can suppress the disease progression in ADPKD model mice.
Methods
Pkd1 gene conditional knockout mice (Pkd1flox/flox Mx-1-Cre mice) were randomly assigned to a control group and a group treated with SCO-792 (SCO group). The control group was fed a normal diet from day 28. The SCO group was fed a diet containing 0.003% (w/w) or 0.01% (w/w) SCO-792. All mice were sacrificed at 56 days of age. We analyzed the cystic phenotype of kidney and liver by measuring kidney or liver/body weight ratio (KW/BW, LW/BW) and cystic index (CI), defined as the percentage of tissue area occupied by cysts. Additionally, we performed immunofluorescence staining and western blotting to evaluate the cyst growth pathways. The inhibitory effect of SCO-792 on amino acids was confirmed by oral protein challenge test in Pkd1flox/flox Mx-1-Cre mice.
Results
In the 0.01% group, KW/BW, LW/BW, and CI were significantly lower than those in the other group. Serum urea nitrogen levels tended to be lower in the 0.01% group. The percentage of Ki-67-positive cells in both kidney and liver was significantly reduced in the 0.01% group. In TUNEL staining of kidney, the percentage of positive cells in the 0.01% group was also significantly decreased. Western blot analysis of kidney revealed a significant downregulation of phosphorylated-S6 protein in the 0.01% group. Although the 0.01% group showed significant weight loss, there was no upregulation of p-AMPK. Oral protein challenge test showed that SCO-792 inhibited amino acids absorption in a dose-dependent manner.
Conclusion
SCO-792 ameliorated cyst growth and preserved kidney function by inhibiting the mTOR pathway activation.
Funding
- Commercial Support – SCOHIA PHARMA, Inc