Development of a new method for prophylaxis and treatment of urinary stone disease is proposed. Since a majority of urinary stones are made of calcium oxalate, the level of urinary oxalate is one of the major risk factors of stone formation. Unfortunately, there is no effective pharmacological treatment of stone disease that targets urinary oxalate concentration. Our method is based on chemical trapping of carbonyl precursors of oxalate biosynthesis and, thus, decreasing urinary oxalate concentration. In the preliminary experiments we have effectively trapped oxalate precursors glycolaldehyde and glyoxylate in vitro, and have reduced urinary oxalate excretion in normal animals (rats). In the current Phase I application we propose to check whether our treatment will result in trapping of oxalate precursors and reduction of urinary oxalate levels in the rat model of hyperoxaluna. If these Phase I experiments demonstrate the feasibility of the proposed approach, in Phase Il we will conduct human studies and optimize our method for patient treatment. Proposed Commercial Applications: Given the frequency of urinary stone disease and high rates of recurrent stone formation, there is a significant market potential for the proposed pharmacological treatment.
Thesaurus Terms: biosynthesis, drug design /synthesis /production, drug screening /evaluation, oxalate, urinary calculi, urinary tract pharmacology, vitamin B6 primary hyperoxaluria, urinary tract disorder chemotherapy atomic absorption spectrometry, fluorescence spectrometry, high performance liquid chromatography, laboratory rat
