Example 14
Cystinuria is a genetic disorder of amino acid import in the kidney characterized by excessive excretion of cystine, and dibasic amino acids (ornitihine, lysine, and arginine) in the urine, and cystine stone formation in the urinary tract.
The potential of a methionine consuming strain described herein to treat, prevent, or reduce cystinuria was evaluated by analyzing the effect of a methionine restricted diet in a Slc3a1 knockout (KO) mouse model for cystinuria. Slc3a1 KO mice were subjected to a reduction in the methionine content of diet from the standard 0.62% to 0.12% for eight weeks, and cysteine as well as cystine levels in urine and plasma, and stone formation in the bladder were evaluated according to a scheme shown in
Cystine stone formation was not observed in any of the twelve mice on the low-methionine diet. In contrast, bladder stones were observed in nine out of twelve mice (75%) on the 0.62% diet. Time of stone formation ranged from 2-8 weeks following diet treatment.
These data suggest that a treatment resulting in a reduction in plasma or urinary methionine, e.g., administration of a methionine-consuming strain described herein, is a promising approach for the treatment of cystinuria.
