This technology includes the use of novel lactate dehydrogenase (LDH) inhibitors, including WO2018005807A1, for the treatment of primary hyperoxalurias (PHs). PHs are rare autosomal recessive disorders caused by overproduction of oxalate, leading to recurrent calcium oxalate kidney stone disease, and in some cases end-stage renal disease. One potential strategy to treat PHs is to reduce the production of oxalate by diminishing the activity of LDH, the proposed key enzyme responsible for converting glyoxylate to oxalate. Biochemical and cell-based assays were used to identify and characterize novel potent inhibitors of LDH that prevent the conversion of glyoxylate to oxalate.
Further clinical work could establish the identified small molecules, including WO2018005807A1, as the active pharmaceutical ingredient (API) for treatments for primary hyperoxalurias.
RNAi therapies targeting LDHA and GO enzymes are currently in clinical trials. Oral delivery of small molecule inhibitors of LDH would be more convenient than repetitive intravenous injections for patients. Small molecule inhibitors also have the advantage of being significantly cheaper to manufacture, thereby being more cost-effective for patients as well.