Therapeutics: Erythropoietin (EPO); DNA methyltransferase; DNA (cytosine-5-)-methyltransferase 1 (DNMT1)
Mouse and cell studies suggest the DNA methyltransferase inhibitor Vidaza azacitidine could help treat anemia associated with chronic kidney disease (CKD). Kidney pericyte-derived myofibroblasts had higher levels of EPO hypermethylation and produced lower levels of EPO in two mouse models of kidney fibrosis than in normal mice. In myofibroblasts from one of the kidney fibrosis models, Vidaza inhibited DNMT1, decreased EPO methylation and increased EPO expression compared with vehicle. In the same mouse model, Vidaza increased plasma levels of EPO and hematocrit, and decreased loss of red blood cells compared with vehicle. Next steps could include testing Vidaza in other models of kidney-disease-related anemia.
Celgene Corp., Pfizer Inc. and Nippon Shinyaku Co. Ltd. market Vidaza to treat myelodysplastic syndrome (MDS). Celgene and Pfizer also market Vidaza to treat acute myelogenous leukemia (AML) and have the compound in Phase I/II testing to treat chronic lymphocytic leukemia (CLL) and Phase I testing to treat B cell lymphoma. ...