Pharmacological approaches in the treatment of primary hyperoxaluria.

Drug therapy receives scant attention as a treatment mode for primary hyperoxaluria (PH). Currently, pyridoxine is the only drug in the arsenal and only a minority of PH1 patients respond to it. In this report a pathway describing the synthesis of glyoxylate, the major precursor of oxalate, is proposed and potential drugs that may be effective in inhibiting hepatic oxalate synthesis are discussed. One of these, (L)-oxothiazolidine-4-carboxylate (OTZ), is currently undergoing evaluation in a Phase II clinical trial. It is suggested that an ideal drug may be an antisense oligonucleotide that blocks the expression of glycolate oxidase, a key enzyme in hepatic oxalate synthesis.