AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency

Pyruvate kinase (PK) deficiency is a rare genetic disease that causes chronic hemolytic anemia. There are currently no targeted therapies for PK deficiency. Here, we describe the identification and characterization of AG-348, an allosteric activator of PK that is currently in clinical trials for the treatment of PK deficiency. We demonstrate that AG-348 can increase the activity of wild-type and mutant PK enzymes in biochemical assays and in patient red blood cells treated ex vivo. These data illustrate the potential for AG-348 to restore the glycolytic pathway activity in patients with PK deficiency and ultimately lead to clinical benefit.

Source: Blood - September 14, 2017 Category: Hematology Authors: Kung, C., Hixon, J., Kosinski, P. A., Cianchetta, G., Histen, G., Chen, Y., Hill, C., Gross, S., Si, Y., Johnson, K., DeLaBarre, B., Luo, Z., Gu, Z., Yao, G., Tang, H., Fang, C., Xu, Y., Lv, X., Biller, S., Su, S.-S. M., Yang, H., Popovici-Muller, J., Sal Tags: Red Cells, Iron, and Erythropoiesis Source Type: research