- In vitro data available
- In vivo data available (animal)
Diabetic nephropathy (DN) is the leading cause of renal failure and is characterized by proteinuria that progresses to renal inflammation and decline in the glornerular filtration barrier (GFB). Podocytes are specialized epithelia cells in the glomerular capsule that have a role in filtration of blood and maintaining the integrity of the GFB; dysfunction of these cells plays a significant role in the pathogenesis of DN. Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose inhibition has beneficial effects in inflammatory diseases.
In the present invention, mice with a podocyte-specific deletion of sEH (pod-sEHKO) were generated to determine the effects of podocyte sEH on renal function. These mice showed moderate improvement in kidney function and systemic glucose homeostasis in normoglycemia and a significant improvement in hyperglycemia. Histology of the kidneys of these animals and in vitro assays with mouse podocytes treated with an sEH inhibitor, confirmed that sEH in podocytes is a key contributor to kidney function and systemic glucose homeostasis. These findings demonstrate that pharmacological and gene-based sEH inhibitors can be used to improve kidney function and blood pressure and protect podocytes from hyperglycemia-induced injury, thus inhibiting or preventing DN.
This invention was co-developed with the University of California at Davis.
- Potential for one or more sEH inhibitors to be use in the treatment of diabetes and DN.
- Basic and clinical research into glucose homestasis and kidney function.
- Novel approach to controlling systemic glucose in diabetes. sEH inhibitors could be used to decrease blood glucose levels in diabetes by increasing glucose clearance in the urine.
- Improve kidney function and blood pressure by protecting podocytes from hyperglycemia-induced injury.
- Beneficial cardiovascular effects, due to their ability to increase serum HDL levels in hyperglycemic conditions.