Office of Technology Development (OTD)

Richard Roman, PhD
Ellis Avner, MD

There is no cure for autosomal dominant polycystic kidney disease (ADPKD). Thus patients reaching end-stage renal disease (ESRD) must seek one of two options for replacing kidney functions: dialysis or transplantation. Prior to ESRD patients are treated for pain, high blood pressure, and urinary tract infections. Likewise, there is no cure for autosomal recessive polycystic kidney disease (ARPKD). The symptoms of autosomal recessive PKD can begin before birth, so it is often called "infantile PKD." Children born with autosomal recessive PKD usually develop kidney failure within a few years. Similar to ADPKD, ARPKD medications can control high blood pressure, antibiotics can control urinary tract infections, and eating increased amounts of nutritious food improves growth. In some cases, growth hormones are used. In response to kidney failure, ARPKD patients must receive dialysis or transplantation.

ADPKD and ARPKD each develop from a different genetic flaw, and each follow a different disease pattern. However, PKD cystic renal epithelia share common phenotypic abnormalities where PKD is characterized by a switch from a well-differentiated, nonproliferative, reabsorptive epithelia to a partially dedifferentiated, secretory epithelia characterized by polarization defects and high rates of proliferation and apoptosis. What is needed in the art is a method of preferentially reducing or inhibiting the proliferation of cystic renal or biliary epithelial cells over the corresponding normal epithelial cells.

The inventors have developed a pharmaceutical method for preferentially reducing the proliferation of cystic epithelial cells in the kidney or bile duct in a human or non-human animal by administering a 20-HETE synthesizing enzyme inhibitor or a 20-HETE antagonist to the human or non-human animal in an amount sufficient to preferentially reduce the proliferation of cystic epithelial cells over normal epithelial cells such as tubule epithelial cells in the kidney or bile duct. The lead compounds can be applied to prevent or treat both ADPKD and ARPKD.

This technology enables the effective treatment of ADPKD and ARPKD. No other pharmaceutical option exists at this time.

The technology has been tested in vitro and in animal studies. Results show that both 20-HETE synthesizing enzyme inhibitor and 20-HETE antagonists effectively prevent and treat ADPKD and ARPKD.