Treatment strategies for glucose-6-phosphate dehydrogenase deficiency: past and future perspectives

Glucose-6-phosphate dehydrogenase (G6PD) maintains redox balance in a variety of cell types and is essential for erythrocyte resistance to oxidative stress. G6PD deficiency, caused by mutations in the G6PD gene, is present in ~400 million people worldwide, and can cause acute hemolytic anemia. Currently, there are no therapeutics for G6PD deficiency. We discuss the role of G6PD in hemolytic and nonhemolytic disorders, treatment strategies attempted over the years, and potential reasons for their failure. We also discuss potential pharmacological pathways, including glutathione (GSH) metabolism, compensatory NADPH production routes, transcriptional upregulation of the G6PD gene, highlighting potential drug targets. The needs and opportunities described here may motivate the development of a therapeutic for hematological and other chronic diseases associated with G6PD deficiency.