Therapeutic targets for paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic and acquired hematopoietic stem cell disorder due to somatic mutations in the PIGA gene, which result in the premature hemolysis of red blood cells (RBCs) in both intra-and extravascular spaces. PNH is characterized by complement-driven destruction of RBCs by the immune system. Currently, hematopoietic stem cell transplanta-tion (HSCT) is the only cure for PNH, albeit carrying a high risk of mortality. With the availability of the C5 inhibitor eculizumab and other complement-targeted pharmaco-therapeutics, HSCT has been relegated to second-line use. Symptomatic therapy may include RBC transfusions, folate, iron and vitamin B12 supplementation, anticoagulation for thrombotic disease, and occasional use of steroids during hemolytic crises. The search for effective treatment strate-gies for PNH continues, with research focusing on the iden-tification of novel targets for drug development. This article presents those drug targets that are currently under active investigation for the treatment of PNH.